WO2007005249A2

WO2007005249A2 - Nanoparticles and dendritic-polymer-based hydrogels comprising them

Info

Publication number: WO2007005249A2
Application number: PCT/US2006/023723
Authority: WO
Inventors: Michael A. Carnahan; Jeffrey A. Clark; Mark W. Grinstaff; Kenneth E. Stockman
Original assignee: Hyperbranch Medical Technology, Inc.
Priority date: 2005-06-29
Filing date: 2006-06-19
Publication date: 2007-01-11
Also published as: WO2007005249A3

Abstract

One aspect of the present invention relates to compositions comprising polymers and nanoparticles that form hydrogels useful as lens replacement materials, lens substitute materials, corneal inlays, and intraocular lenses. The hydrogels of the invention can be formed using a polyacrylate, silicone, or dendritic macromolecule. In certain instances, the hydrogels of the invention comprise nanoparticles ranging in diameter from about 0.1 nm to about 100 nm. The nanoparticles are generally dispersed throughout the hydrogel and may be covalently or noncovalently crosslinked. The nanoparticles may be made of a metal, metal oxide, or ceramic. In certain instances, the nanoparticles comprise a ceramic core coated with a layer of silica. Another aspect of the present invention relates to a method of forming a lens composition comprising treating a mixture of a polymerizable dendrimeric compound and nanoparticles with a polymerization agent. Another aspect of the present invention relates to a nanoparticle comprising a core coated with a layer of silica. In certain instances, the core is made of a metal, metal oxide, or ceramic. Another aspect of the invention relates to a kit for forming a lens comprising a polymerizable dendrimeric compound, nanoparticles, and a system for delivering the dendrimeric compound and nanoparticles to the lens bag of a patient.

Description

Nanoparticles and Dendritic-Polymer-Based Hydrogels Comprising Them

Background of the Invention

Nanoparticles Nanoparticles are small particles typically ranging in size from about one nanometer to several hundred nanometers in diameter. Many nanoparticles exhibit interesting properties, e.g., high refractive index, due to their size and composition. The small size of nanoparticles allows them to be useful for producing a variety of products such as dyes and pigments; tools for biological discovery, medical imaging, and therapeutics; magnetic recording media; quantum dots; and even uniform and nanosize semiconductors.

A large number of methods have been reported for preparing nanoparticles. Nanoparticles have been prepared using an evaporation and condensation method. More recent reports describe the preparation of nanoparticles using sonochemical processing, cavitation processing, microemulsion processing, high-energy ball milling, and aerosol- based methods, such as combustion flame, plasma, laser ablation, chemical vapor condensation, spray pyrolysis, electrospray, and plasma spray.

Despite the previous reports of nanoparticles and methods of making nanoparticles, many nanoparticles made of metal or a metal oxide suffer from the limitation that they tend to agglomerate in aqueous solutions. For example, nanoparticles made of TiO₂ or ZnO₂ are generally only dispersed in aqueous solutions that have a pH greater than about 8 or a pH less than about 5. The fact that many nanoparticles may agglomerate has, not been a significant problem for many previous uses of nanoparticles because the previous uses did not require a disperse, optically-clear composition. However, compositions comprising nanoparticles for use in opthamalic applications should be clear. Therefore, the need exists for nanoparticle compositions that are optically clear.

Refractive surgery — Lens Replacement

The lens is the part of the eye that helps focus light on the retina, which in turn sends the visual signal to the brain. To produce a sharp image, the lens must remain clear and free of defects. Defects in the lens may cause vision problems requring that the lens be replaced with a synthetic material. For example, a natural lens may need to be replaced when a cataract or other disease causes the lens to function poorly. A cataract is a clouding of the lens in the eye that can cause vision problems. A natural lens may also need to be replaced when a patient suffers an eye injury that causes damage to the lens.

The optical properties of the normal eye lens are the consequence of a high concentration of proteins called "crystallins" forming a natural hydrogel. In vertebrate lenses, a range of differently sized protein assemblies, the alpha-, beta- and gamma- crystallins, are found creating a medium of high refractive index. The anatomical basis of accommodation includes the lens substance, lens capsule, zonular fibers, ciliary muscle and the elastic part of the choroid. Accommodation occurs through accurately controlled adjustments in the shape and thickness of the lens. The capsular bag is essential in transmitting the various extralenticular forces to the lens substance.

Modern cataract surgery can be done through a small incision (usually 2.5-3.5 mm). Once the incision is made, the anterior chamber is filled with a viscoelastic and the capsular bag is pricked with a needle. From this incision, a small continuous circular capsulorhexis (CCC) approximately 1.5 mm in diameter is performed using capsulorhexis forceps. Next endocapsular phacoemulsification is performed and the lens epithelial cells are removed by aspiration.

Since removing the cataract leaves the eye without a lens to focus light, an artificial (intraocular) lens is commonly placed inside the eye. Most intraocular lenses are made of plastic, silicone, or acrylic compounds; have no moving parts; and last for the remainder of a person's life. These intraocular lens implants are held in place by the posterior capsule are not able to provide ocular accommodation.

IOL Materials Preferred intraocular lens (IOL) materials include plastics, gels or hydrogels. IOL implants that are softer, more flexible are generally favored due to their ability to be compressed, folded, rolled or otherwise deformed. Such softer IOL implants may be deformed prior to insertion through an incision in the eye. Following insertion of the IOL in an eye, the IOL returns to its original pre-deformed shape due to the memory characteristics of the soft material. Softer, more flexible IOL implants can be implanted through a smaller incision than that required for more rigid IOLs, i.e., 5.5 to 7.0 mm. Despite these advantages, the high water content of hydrophilic acrylics, or "hydrogels," affords IOLs with a relatively low refractive indice. The more rigid IOL implants suffer from the disadvantage that larger incisions are required, which have been found to be associated with an increased incidence of postoperative complications, such as induced astigmatism.

A high refractive index is also a desirable feature in the production of IOLs in order to impart high optical power with a minimum of optic thickness. By using a material with a high refractive index, visual acuity deficiencies may be corrected using a thinner IOL. A thin IOL minimizes potentially harmful contacts between the IOL and internal structures of the eye, such as the iris.

Examples of materials that may be used in the preparation of an intraocular lens are reported in US 6,881,809 and US 6,398,809. In US 6,881,809, Salamone et al. described polymeric compositions produced through the polymerization of one or more aromatic-based silyl monomers or the copolymerization of one or more aromatic-based silyl monomers with one or more aromatic or non-aromatic non-siloxy-based monomers, hydrophobic monomers or hydrophilic monomers. These aromatic monomers were added to increase the refractive index. In US 6,398,809, Hoffmann et al. describe foldable or compressible materials, such as silicone polymers, hydrocarbon and fluorocarbon polymers, hydrogels, soft acrylic polymers, polyesters, polyamides, polyurethane, silicone polymers with hydrophilic monomer units, fluorine-containing polysiloxane elastomers and combinations thereof.

Accommodating IOL materials

Despite the fact that researchers have been investigating IOL materials since at least the I960' s, there are no adequate materials for an accommodating IOL. Materials for an accommodating IOL or endocapsular lens should have an elastic modulus and relaxation time that is constant. The material should also be comparable to a youthful lens (approximately 1.0 kPa). In addition, the material should maintain nearly full optical transmission at a relatively high refractive index (1.41-1.42) and exhibit minimal swelling once the material, e.g., polymer, is cured. Several research groups have reported candidate polymers for accommodating IOLs, which are listed below. However, at present, there are no materials that meet all the foregoing requirements for IOL materials In 1964, Kessler reported one of the first examples of removing a natural lens and refilling with a synthetic compound to provide accommodation. Kessler used Carquille's immersion oil, silicone fluids, damar gum, Silastics, RTV S-5395, and RTV S-5396 as refilling materials to form the physical gels under physiological temperatures. [Kessler, 1964 #17;Kessler, 1966 #32] Kessler's reports demonstrated that a lens capsule could be refilled with a transparent substance both in vitro and in vivo. However, even the best materials used in the reports had a low refractive index, slow cure times, and the mechanical properties were too high.

Parel et al. utilized filler-free divinylmethylcyclosiloxane, [Parel, 1986 #16;Haefliger, 1987 #15;Haefliger, 1994 #12], a chemical cross-linker, and other silicone compounds [Haefliger, 1987 #15;Yonemura, 1993 #14], with RIs of 1.402, to form the silicone elastomers. Parel's group reported favorable mechanical properties and anterior chamber shallowing, indicating restoration of some accommodation, but the presence of lens epithelial cells was a major hindrance in obtaining accurate information for the degree of accommodation.

Nishi et al. used a polymethyldisiloxane liquid containing a hydrogen polysiloxane crosslinking agent with a silicone plug for sealing the capsular opening to prevent leakage of the injected material. Major obstacles included the appearance of posterior capsular opacification (PCO), and some small leaking which was reported to be surgically removed. [Nishi, 1998 #21] Previously, Nishi had used a balloon inserted into the capsule, which was filled with polymer, but found that it did not match the shape of the capsular bag well enough, and is currently using a plug to seal the capsule. [Sakka, 1996 #27]

Silicones generally have a low specific gravity, and PCO has been reported to be a complication. Hettlich et al. reported endocapsular polymerization in which a monomer mixture was injected and photopolymerized in situ to form the gel. [Hettlich, 1994 #38]

The toxicity of unreacted monomers and the exothermic nature of the polymerization reaction were indicated as potential risks to living tissues. Jacqueline et al. reported the endocapsular photogelation of acrylate modified N-vinylpyrolidone/vinyl alcohol copolymer using acrylamide-based photoinitiator. [de Groot, 2001 #31] Recently, isocyanate crosslinked hydrogels from polyalcohols were investigated for accommodative intraocular lens with suitable refractive index, [de Groot, 2003 #33; de Groot, 2002 #34] Koopmans et al. demonstrated the possibility of restoration of lens power changes with mechanical stretching upon refilling human lenses using polymeric silicone materials. [Koopmans, 2003 #30] Lee et al. evaluated the use of a poloxamer hydrogel as an accommodating IOL.

Although the refractive index was low, a technique for injecting the material in vivo was developed, which exhibited favorable short term results. [Han, 2003 #20] Ravi et al. investigated water-soluble acrylamide copolymers containing pendant thiol groups that were oxidized to form gels within the lens capsular bag. See [Aliyar, 2005 #26;Aliyar, 2005 #25]. However, the refractive index of the gel was low and swelling and toxicity data were not reported. A reversible hydrogel based on acrylamide is also described by Ravi in U.S. Patent Application 20040156880.

Summary of the Invention

One aspect of the present invention relates to compositions comprising polymers and nanoparticles that form hydrogels useful as lens replacement materials, lens substitute materials, corneal inlays, and intraocular lenses. The hydrogels of the invention are superior materials for ophthalmologic applications because they can form transparent, stable, high refractive-index composites. The hydrogels of the invetion can be formed using a polyacrylate, silicone, or dendritic macromolecule. In a preferred embodiment, the polymer is a dendritic macromolecule. The lens may be formed in situ by injecting a solution containing the materials to form the hydrogel into an empty lens capsule. Once injected, the materials polymerize to form a hydrogel mimic of the natural lens. Alternatively, the lens may be formed ex vivo and then implanted as a thin disk-shaped material. In certain instances, the hydrogels of the invention comprise nanoparticles ranging in diameter from about 0.1 nm to about 100 nm. The nanoparticles are generally dispersed throughout the hydrogel and may be covalently or noncovalently crosslinked. The nanoparticles may be made of a metal, metal oxide, or ceramic. In certain instances, the nanoparticles comprise a ceramic core coated with a layer of silica.

The hydrogels of the invention may be reversible or non-reversible. In a preferred embodiment, the hydrogel is non-reversible. In certain instances, the lens is sterilzed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration. The sterilized lens is then delivered in vivo using a sterile delivery device, such as a syringe or other applicator.

Another aspect of the present invention relates to a method of forming a lens composition comprising treating a mixture of a polymerizable dendrimeric compound and nanoparticles with a polymerization agent. In certain instances, the polymerization agent is ultraviolet or visible light. In certain instances, the method of the invention further comprises the step of delivering a mixture comprising the hydrogel-forming components to the lens bag of a patient. In a prefered embodiment, the nanoparticles are a metal oxide or ceramic coated with a layer of silica.

Another aspect of the present invention relates to a nanoparticle comprising a core coated with a layer of silica. In certain instances, the core is made of a metal, metal oxide, or ceramic. In a preferred embodiment, the core is made of a ceramic. Another aspect of the invention relates to a kit for forming a lens comprising a polymerizable dendrimeric compound, nanoparticles, and a system for delivering the dendrimeric compound and nanoparticles to the lens bag of a patient. In certain instances, the kit further comprises a desiccant and a syringe. In certain instances, the kit further comprises a polymerization agent.

Brief Description of the Figures

Figure 1 depicts various monomers that can be used to prepare dendrimers used in the invention. Figure 2 depicts various monomers that can be used to prepare dendrimers used in the invention.

Figure 3 depicts various monomers that can be used to prepare dendrimers used in the invention.

Figure 4 depicts various monomers that can be used to prepare dendrimers used in the invention.

Figure 5 depicts various monomers that can be used to prepare dendrimers used in the invention.

Figure 6 depicts various monomers that can be used to prepare dendrimers used in the invention. Figure 7 depicts various monomers that can be used to prepare dendrimers used in the invention.

Figure 8 depicts a dendrimer terminated with nucleoside groups amenable to the invention.

Figure 9 depicts dendrimers and compounds useful for making dendrimers amenable to the present invention. Figure 10 depicts a dendrimer amenable to the present invention.

Figure 11 depicts photocrosslinkable PEG₃₄Oo-(PGLS A-M A₄)₂ macromer 1 for hydrogel formation.

Figure 12 depicts a double-acting, single-barrel syringe. Figure 13 depicts a double-barrel syringe.

Detailed Description of the Invention

Aspects of the present invention relate to nanoparticles and compositions comprising nanoparticles, where the nanoparticles afford an optically-clear, high refractive index composition when dispersed in an aqueous solution at neutral pH. The nanoparticles may be coated to achieve desirable physical properties. For example, TiO₂ particles coated with lactic acid or a silane derivate were prepared. The coated TiO₂ particles remained dispersed in an aqueous solution at neutral pH. The metal-oxide nanoparticles of the invention can be entrapped in a hydrogel at neutral pH. The hydrogel is useful in ophthalmic applications. Accordingly, aspects of the present invention also include the preparation and use of nanoparticles in ophthalmic applications. More specifically, one aspect of the present invention relates to hydrogel compositions comprising nanoparticles for use as endocapsular lenses, intraocular lenses, or contact lenses; and methods of preparing the hydrogel compositions. The hydrogel compositions can be used in clinical applications, such as restoring vision using a synthetic lens. In certain instances, the hydrogel compositions of the invention are used as a synthetic lens material for restoring vision after a cataract procedure. The hydrogel may comprise crosslinkable polymers, such as dendritic macromolecules. The nanoparticles can be either noncovalently or covalently crosslinked. Furthermore, the nanoparticles can be dispersed throughout the hydrogel-nanoparticle composite. In certain instances, the hydrogel composition can be formed in vitro, in vivo, or in situ.

In certain instances, the compositions used to create the lens comprise a dendrimer and nanoparticle. In certain aspects of the invention, the dendrimer has an acrylate group attached at the periphery of the dendrimer. Treating acrylated-capped dendrimers with ultraviolet radiation or a radical inititiator in the presence of nanoparticles causes the dendrimers to polymerize forming a hydrogel-nanoparticle endocapsular lens, intraocular lens, or contact lens. In certain instances, the dendritic polymers comprise a lysine, cysteine, or isocysteine residue or other nucleophilic group attached to the periphery of the dendrimer. Addition of a compound containing two or more electrophilic groups, such as an aldehyde, activated ester, or acrylate, to the lysine-capped, cysteine-capped, or isocysteine- capped dendrimers in the presence of nanoparticles produces a polymeric compound that can form a endocapsular lens, intraocular lens, or contact lens. In certain instances, the compositions used to form the lens comprise nanoparticles and a compound that has a poly(lysine) core to which cysteine or isocysteine groups or other nucleophilic groups are attached; and the composition is then added to a compound containing an electrophilic group, such as an aldehyde, activated ester, or acrylate, to produce a polymeric endocapsular lens, intraocular lens, or contact lens.

Crosslinking, such as with a methacrylated functionalized denditic polymer, can be achieved using a photochemical or chemical reaction or a combination of both. An embodiment of this invention is the preparation of crosslinkable biodendritic macromolecules that can undergo a covalent or non-covalent crosslinking reaction to form a three-deminsional crosslinked gel or network, wherein the crosslinking reaction does not involve a single or multi-photon process (i.e., light). The dendritic polymer can be used for the encapsulation or the covalent attachment of pharmaceutical agents, such as bioactive peptides (e.g., growth factors), antibacterial compositions, antimicrobial compositions, and antiinflammatory compounds to aid in the clinical outcome. In certain instances, the pharmaceutical agent causes a reduction or prevention of posterior capsule opacification (PCO).

A further embodiment of this invention is the use of a dendritic polymer and nanoparticle to afford a synthetic hydrogel lens or lens material in situ. The crosslinkable formulation is injected via a small opening into an empty lens-capsule bag. Subsequent crosslinking by a photochemical or chemical reaction affords a hydrogel lens. Alternatively, the crosslinked hydrogel can be prepared, and then this preformed lens can be injected in the empty lens bag. In the latter case, the preformed lens can be pre-extracted to remove impurities and pre-swollen. Also, these dendritic polymers can be combined with conventional IOL materials, such as acrylates, and used in a cataract or other lens removal and replacement procedure. An additional embodiment is the use of the branched structures, aromatic amino acids, other aromatics, or heterocycles into the dendritic structure to increase the refractive index. As mentioned above, nanoparticles (2-25 nm) can be added to the resulting polymeric endocapsular lens, intraocular lens, or contact lens at a weight percent of 1% to 35% in order to alter the refractive index. The nanoparticles can be either non-covalently or covalently crosslinked throughout the composite. The above nanoparticles/hydrogel compositions can be used in conjunction with a polymer plug to close the capsulorrhexis. The lens material can be injected through the plug or the plug can be put into place after the lens has been inserted.

The lens compositions of the invention can also be formed by combining nanoparticles with polymers, such as a silicone, acrylic, polymethylmethacrylate (PMMA), block copolymers of styrene-ethylene-butylene-styrene (C-FLEX) or other styrene-base copolymers, polyvinyl alcohol (PVA), polyurethanes, or polymers comprising polyacrylates, e.g., PHE.

Dendritic Macromolecules

Dendritic polymers are globular monodispersed polymers composed of repeated branching units emitting from a central core. (U.S. 5714166; U.S. 4289872; U.S. 4435548; U.S. 5041516; U.S. 5362843; U.S. 5154853; U.S. 05739256; U.S. 5602226; U.S. 5514764; Bosman, A. W.; Janssen, H. M.; Meijer, E. W. Chem. Rev. 1999, 99, 1665-1688. Fischer, M.; Vogtle, F. Angew. Chem. Int. Ed. 1999, 38, 884-905. Zeng, F.; Zimmerman, S. C. Chem. Rev. 1997, 97, 1681-1712. Tomalia, D. A.; Naylor, A. M.; Goddard, W. A. Angew. Chem. Int. Ed. Engl. 1990, 29, 138.) These macromolecules are synthesized using either a divergent (from core to surface) (Buhleier, W.; Wehner, F. V.; Vogtle, F. Synthesis 1987, 155-158. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. Polymer Journal 1985, 17, 117-132. Tomalia, D. A.; Baker, H.; Dewald, J.; Hall, M.; Kallos, G.; Martin, S.; Roeck, J.; Ryder, J.; Smith, P. Macromolecules 1986, 19, 2466. Newkome, G. R.; Yao, Z.; Baker, G. R.; Gupta, V. K. J. Org. Chem. 1985, 50, 2003.) or a convergent approach (from surface to core). See Hawker, C. J.; Frechet, J. M. J. J. Am. Chem. Soc. 1990, 112, 7638-7647. This research area has undergone tremendous growth in the last decade since the early work of Tomalia and Newkome. Compared to linear polymers, dendrimers are highly ordered, possess high surface area to volume ratios, and exhibit numerous end-groups for functionalization. Consequently, dendrimers display several favorable physical properties for both industrial and biomedical applications including: small polydispersity indexes (PDI), low viscosities, high solubility and miscibility, and excellent adhesive properties. The majority of dendrimers investigated for biomedical/biotechnology applications (e.g., MRI, gene delivery, and cancer treatment) are derivatives of aromatic polyether or aliphatic amides, and thus are not ideal for in vivo uses. See Service, R. F. Science 1995, 267, 458- 459. Lindhorst, T. K.; Kieburg, C. Angew. Chem. Int. Ed. 1996, 35, 1953-1956. Ashton, P. R.; Boyd, S. E.; Brown, C. L.; Yayaraman, N.; Stoddart, J. F. Angew. Chem. bit. Ed. 1997, 1997, 732-735. Wiener, E. C; Brechbeil, M. W.; Brothers, H.; Magin, R. L.; Gansow, O. A.; Tomalia, D. A.; Lauterbur, P. C. Magn. Reson. Med. 1994, 31, 1-8. Wiener, E. C; Auteri, F. P.; Chen, J. W.; Brechbeil, M. W.; Gansow, O. A.; Schneider, D. S.; Beldford, R. L.; Clarkson, R. B.; Lauterbur, P. C. J. Am. Chem. Soc. 1996, 118, 7774-7782. Toth, E.; Pubanz, D.; Vauthey, S.; Helm, L.; Merbach, A. E. Chem. Eur. J. 1996, 2, 1607-1615. Adam, G. A.; Neuerburg, J.; Spuntrup, E.; Muhl;er, A.; Scherer, K.; Gunther, R. W. J. Magn. Reson. Imag. 1994, 4, 462-466. Bourne, M. W.; Margerun, L.; Hylton, N.; Campion, B.; Lai, J. J.; Dereugin, N.; Higgins, C. B. J. Magn. Reson. Imag. 1996, 6, 305-310. Miller, A. D. Angew. Chem. Int. Ed. 1998, 37, 1768-1785. Kukowska-Latallo, J. F.; Bielinska, A. U.; Johnson, J.; Spinder, R.; Tomalia, D. A.; Baker, J. R. Proc. Natl. Acad. ScL 1996, 93, 4897-4902. Hawthorne, M. F. Angew. Chem. Int. Ed. 1993, 32, 950-984. Qualmann, B.; Kessels M.M.; Musiol H.; Sierralta W.D.; Jungblut P.W.; L., M. Angew. Chem. Int. Ed. 1996, 35, 909-911.

Biodendrimers are a novel class of dendritic macromolecules composed entirely of building blocks known to be biocompatible or are natural metabolites in vivo. Biodendrimers may or may not be degradable. One aspect of the present invention relates to the synthesis, characterization, and use of novel dendrimers and dendritic macromolecules called

"biodendrimers or biodendritic macromolecules." In certain instances, the dendrimers of the present invention comprise biocompatible or natural metabolite monomers such as glycerol, lactic acid, glycolic acid, succinic acid, ribose, adipic acid, malic acid, glucose, citric acid, glycine, lysine, cysteine, alanine, etc. A further embodiment of the invention is a dendritic structure that possess glycerol and one or more of lactic acid, glycolic acid, succinic acid, ribose, adipic acid, malic acid, glucose, citric acid, glycine, lysine, cysteine, alanine, and the like as a building block. An additional embodiment of the invention relates to a dendrimer comprising all lysine resides such that it is a generation one or higher or a lysine dendritic macromolecule terminated with cystene residues such that it is a generation one or higher.

These biodendritic macromolecules are useful for preparing an ophthalmic lens. The polymers used in the hydrogels of the present invention may be dendritic polymers or copolymers of polyesters, polyethers, polyether-esters, and polyamino acids, polyurethanes, etc or combinations thereof. Careful selection of the monomer, linkage, size, and generation number permits controll over the degradation rate of the polymer. Thus, one aspect of the present invention relates to dendritic polymers and copolymers of polyesters and polyamino acids, polyethers, polyurethanes, polycarbonates, polycarbamates, polyamino alcohols or combinations of these polymer classess that are chemically modified for different biomedical applications, such as ophthalmic lens. It is a further aspect of the invention to provide dendritic polymers and copolymers of polyesters and polyamino acids with improved properties such as limited, or no, biodegradability, biocompatibility, and mechanical strength. It is still another aspect of the invention to provide dendritic polymers that can be derivatized to include functionalities such as peptide sequences or growth factors to improve the interaction of the polymer with cells and tissues.

The dendritic polymers of the invention provide numerous advantages including multiple end-groups for functionalization, crosslinked gels with high crosslinking densities at low polymer concentration, globular structure, low viscosities, and a well-defined composition. In contrast to the dendritic polymers of the invention, the properties of conventional linear polymers often cannot be easily controlled or modified because they (e.g., PLA) do not possess functional groups, other than end groups, permiting chemical modification. Conventional polymers also suffer from the disadvantage that they do not adopt a well- defined structure in solution.

Dendritic polymers described herein can be used with linear polymers at ratios of 0.1 to 99.9% to afford ophthalmic lens materials that possess good optical, mechanical, and degradation properties. Thus, another aspect of the present invention is the use of linear polyacrylates and siloxanes, silicones, acrylics, polymethylmethacrylate (PMMA), block copolymers of styrene-ethylene-butylene-styrene (C-FLEX) or other styrene-base copolymers, polyvinyl alcohol (PVA), polyurethanes, or any other suitable polymers or monomers polyacrylates (e.g., PHE) in combination with dendritic polymers. The linear polymers can also be block copolymers. A prefered example of a linear polymer is a copolymer of 2-hydroxyethyl methacrylate (HEMA) and 6-hydroxyhexyl methacrylate (HOHEXMA), i.e., poly(H£M4-co-HOHEXMA).

One aspect of the present invention relates to an in situ, ex vivo, in vitro, or in vivo method for preparing and administrating a biocompatible gel, comprising: (a) forming a reactive composition by admixing a biocompatible crosslinking polymer having two different nucleophilic groups, such as sulfhydryl and amine groups where there is at least one amine or sulfhydryl group on the polymer with a biocompatible crosslinking polymer B having amine- and sulfhydryl-reactive groups, and further wherein the amine- and sulfhydryl- reactive groups are capable of covalent reaction with the amine and sulfhydryl groups upon admixture of polymers A and B under effective crosslinking conditions to form a gel in less than one day; and (b) allowing the components of the reactive composition to crosslink and thereby form a gel.

Another aspect of the present invention relates to dendritic or branched polymers or copolymers composed of monomers synthesized by combining branching compounds with other linear or branched building blocks. Both components are known to be biocompatible or are natural metabolites in vivo including but not limited to glycerol, citric acid, lactic acid, glycolic acid, adipic acid, caproic acid, ribose, glucose, succinic acid, malic acid, amino acids, peptides, synthetic peptide analogs, poly(ethylene glycol), poly(hy.droxyacids) [e.g., PGA. PLA], including where one of the monomers is a branched structure such as glycerol combined with one of the other components.

In certain instances, the present invention relates to the aforementioned polymers derivatized with peripheral compounds possessing an olefin, including, but not limited to, acrylate and methacrylate.

In certain instances, the present invention relates to the the aforementioned polymers derivatized with peripheral compounds, including, but not limited to, cysteine, lysine, other amino acids, or any other compounds that would provide terminal nucleophiles (including, but not limited to, amines, thiols, hydroxyl groups) or electrophiles (including but not limited to NHS esters, maleimides, aldehydes, ketones).

In certain instances, the present invention relates to the the aforementioned polymers for subsequent polymerization/crosslinking/reaction with another linear or branched structure with either olefinic, electrophilic or nucleophilic groups, respectively to form a gel.

In certain instances, the present invention relates to the the aforementioned polymers for subsequent polymerization/crosslinking/reaction with another linear or branched structure via a photopolymerization process (single or multi-photon process) to form a gel. Another aspect of the present invention relates to a branching structure with at least three functional groups composed of, but not limited to, glycerol, citric acid, malic acid, amino acids, peptides, synthetic peptide analogs, or other dendritic strucutures synthesized to produce terminal olefins (including, but not limited to, acrylate or methacrylate groups), nucleophiles (including but not limited to amines, thiols, hydroxyl groups) or electrophiles (including but not limited to NHS esters, maleimides, aldehydes, ketones) for subsequent polymerization/crosslinking with another linear or branched structure with either olefmic, electrophilic or nucleophilic groups, respectively.

Another aspect of the present invention relates to a branching structure with at least three functional groups composed of but not limited to glycerol, citric acid, malic acid, amino acids, peptides, synthetic peptide analogs, or other dendritic structures derivatized with peripheral compounds including, but not limited to, cysteine, lysine, other amino acids, or any other compounds that would provide terminal olefins (including, but not limited to, acrylate or methacrylate groups), nucleophiles (including, but not limited to, amines, thiols, and hydroxyl groups) or electrophiles (including but not limited to NHS esters, maleimides, aldehydes, and ketones) for subsequent polymerization/crosslinking with another linear or branched structure with either olefinic, electrophilic or nucleophilic groups, respectively.

Another aspect of the present invention relates to a branching structure composed of three lysine amino acids with four cysteine amino acids on the periphery with the structure CysLys(Cys)Lys(CysLys(Cys))OMe*4HCl as described in the examples.

Another aspect of the present invention relates to a branching structure composed of three lysine amino acids with amines on the periphery with the structure (Lys)Lys(Lys)OMe»4HCl as described in the examples.

In certain instances, the present invention relates to the aforementioned polymers for subsequent polymerization/crosslinking/reaction with another linear or branched structure with olefinic, electrophilic or nucleophilic groups to form a gel.

In certain instances, the present invention relates to the aforementioned polymers for subsequent polymerization/crosslinking/reaction with another linear or branched structure through thiazolidine linkages to form a gel. In certain instances, the present invention relates to the aforementioned polymers undergoing polymerization/crosslinking with a poly(ethylene glycol) molecular weight of about 200 to about 200,000 with at least two electrophilic groups. In certain instances, the present invention relates to the aforementioned polymers undergoing polymerization/crosslinking with a ρoly(ethylene glycol) molecular weight of about 200 to about 200,000 with at least two nucleophilic groups.

In certain instances, the present invention relates to the aforementioned polymers undergoing polymerization/crosslinking with a poly(ethylene glycol) molecular weight of about 200 to about 200,000 with functional groups including, but not limited to, olefins, aldehydes, maleimides, or NHS esters.

In certain instances, the present invention relates to the aforementioned polymers undergoing polymerization/crosslinking with a poly(ethylene glycol) molecular weight of about 200 to about 200,000 with aldehyde functional groups to form hydrogels through the formation of thiazolidine linkages.

In certain instances, the present invention relates to the the aforementioned formulations in which each of the components are dissolved or suspended in an aqueous solution wherein the said aqueous solution is selected from water, buffered aqueous media, saline, buffered saline, solutions of amino acids, solutions of sugars, solutions of vitamins, solutions of carbohydrates or combinations of any two or more thereof.

In certain instances, the present invention relates to the application of the aforementioned formulation through a delivery device which physically separates the components until the components are physically mixed by the end user, including, but not limited to, a dual barrel syringe with a mixing device.

Another aspect of the present invention relates to packaging of the aforementioned branching compounds in an aqueous solution at a preselected pH and molarity selected from the aqueous solutions described above and the packaging of the second compound in an aqueous solution at another preselected pH and molarity selected from the aqueous solutions described above. When combined, the pH and molarities of the two solutions produce a final desired solution with a different pH.

Another aspect of the present invention relates to packaging of the aforementioned branching compounds in an aqueous solution at a preselected pH and molarity selected from the aqueous solutions described above and the packaging of the second compound in an aqueous solution at another preselected pH and molarity selected from the aqueous solutions described above. The contents are packaged free of oxygen and shielded from light. When combined, the pH and molarities of the two solutions produce a final desired solution with a different pH.

Another aspect of the present invention relates to packaging of the aforementioned branching compounds as a powder and adding an aqueous solution at a preselected pH and molarity selected from the aqueous solutions described above before use. The second component may either be packaged by dissolving the second compound in an aqueous solution at another preselected pH and molarity selected from the aqueous solutions described above or packaged similar to the first compound in which the compound stored as a powder and an aqueous solution at a preselected pH and molarity selected from the aqueous solutions described above is added before use. The contents are packaged free of oxygen and shielded from light. When combined, the pH and molarities of the two solutions produce a final desired solution with a different pH.

Another aspect of the present invention relates to the storage of the aforementioned cystein-terminated polymers in an acidic, oxygen-free solution to minimize the formation of disulfide bonds.

Another aspect of the present invention relates to the storage of the aforementioned aldehyde-terminated polymers in an acidic, oxygen-free solution to maximize the percent reactivity of the polymer and minimize aldol condensation and reverse Michael additions. Another aspect of the present invention relates to the addition of various additives that might be incorporated into the polymer formulations including, but not limited to, antioxidants, colorants, viscosity modifiers, plasticizers, small molecule carbohydrates, large molecule carbohydrates, amino acids, peptides, or other water soluble polymers (linear or branched). Such additives may be added to increase the shelf life, increase the polymerization rate, modifiy the pH or molarity of the solution, change the refractive index, modify the mechanical properties, change crosslinking density, decrease swelling, or aid in visualization.

Another aspect of the present invention relates to the addition of various additives or antimicrobial agents such has polyhexamethylene biguanide (PHMB) that might be incorporated into the polymer formulations. Another aspect of the present invention relates to the resulting hydrogels formed by mixing the aforementioned compounds as described and prepared above. In certain instances, the present invention relates to hydrogels formed by photopolymerization of the aforementioned compounds.

Another aspect of the present invention relates to a method of using crosslinkable/polymerizable/reactionary dendritic polymers, branching structures, and their hydrogels for delivery of therapeutics.

Another aspect of the present invention relates to a crosslinkable/polymerizable/reactionary dendritic polymer or monomer wherein the crosslinking is of covalent, ionic, electrostatic, and/or hydrophobic nature.

Another aspect of the present invention relates to a crosslinkable dendritic polymer or monomer wherein the crosslinking reaction involves a nucleophile and electrophile.

Another aspect of the present invention relates to a crosslinkable dendritic polymer or monomer wherein the crosslinking reaction is a photochemical reaction using a UV or visible photoinitiator chromophore.

Another aspect of the present invention relates to a method of using a crosslinkable branched or dendritic polymer combined with a crosslinkable small molecule(s) (molecular weight less than about 1000 daltons) for a medical or tissue engineering application.

Another aspect of the present invention relates to a crosslinkable branched or dendritic polymer or monomer wherein the said crosslinking dendritic polymer is combined with one or more linear, comb, multi-block, star polymers or crosslinkable comb, multi- block, star polymers.

Another aspect of the present invention relates to the aforementioned polymers, branching structures, and their resulting hydrogels wherein the polymer or crosslinkable monomer is D or L configuration or a mixture.

Another aspect of the present invention relates to the aforementioned polymers, branching structures, and their hydrogels wherein the dendritic structure is asymmetric at the surface such as a surface block structure where a carboxylate acid(s) and alkyl chains, or acrylate(s) and PEG(s) are present, for example, or within the core and inner layers of the dendrimer such as amide and ester linkages in the structure.

Another aspect of the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer wherein the polymer is a star biodendritic polymer or copolymer as shown in at least one of the formulas below: where Y and X are the same or different at each occurrence and are O, S, Se, N(H), or P(H) and where Rj, R₂, R₃, R₄, R₅ R₆, R₇, R₈, A or Z are the same or different and include -H, -CH₃, -OH, carboxylic acid, sulfate, phosphate, aldehyde, methoxy, amine, amide, thiol, disulfide, straight or branched chain alkane, straight or branched chain alkene, straight or branched chain ester, straight or branched chain ether, straight or branched chain silane, straight or branched chain urethane, straight or branched chain, carbonate, straight or branched chain sulfate, straight or branched chain phosphate, straight or branched chain thiol urethane, straight or branched chain amine, straight or branched chain thiol urea, straight or branched chain thiol ether, straight or branched chain thiol ester, or any combination thereof.

Another aspect of the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer where the straight or branched chain is of about 1-50 carbon atoms wherein the chain is fully saturated, fully unsaturated or any combination therein In certain instances, the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer where the straight or branched chain is of about 1-50 carbon atoms wherein the chain is fully saturated, fully unsaturated or any combination therein.

In certain instances, the present invention relates to the aforementioned crosslinlcable or noncrosslinkable polymer wherein straight or branched chains are the same number of carbons or different wherein R₁, R₂, R₃, R₄, Rs.Rβ, R₇, R₈, A or Z are any combination of the linkers including ester, silane, urea, amide, amine, carbamate, urethane, thiol-urethane, carbonate, thio-ether, thio-ester, sulfate, phosphate and ether.

In certain instances, the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer which includes at least one chain selected from the group consisting of hydrocarbons, flourocarbons, halocarbons, alkenes, and alkynes.

In certain instances, the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer which includes at least one chain selected from the group consisting of linear and dendritic polymers. In certain instances, the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer wherein said linear and dendritic polymers include at least one selected from the group consisting of polyethers, polyesters, polyamines, polyacrylic acids, polycarbonates, polyamino acids, polynucleic acids and polysaccharides of molecular weight ranging from about 200-1,000,000, and wherein said chain contains 0, 1 or more than 1 photopolymerizable group.

Another aspect of the present invention relates to a crosslinkable or noncrosslinkable polymer, wherein the polyether is PEG, and wherein the polyester is PLA, PGA or PLGA.

Another aspect of the present invention relates to a linear polymer wherein the chain is a polymer or copolymer of a polyester, polyamide, polyether, or polycarbonate of or the aforementioned polymer in combination with a polyester, polyamide, polyether, or polycarbonate of:

Structure I

Structure II

Structure III In certain instances, the present invention relates to the aforementioned polymer comprised of repeating units of general Structure I, where A is O, S, Se, or N-R₇.

In certain instances, the present invention relates to the aforementioned polymer, where W, X, and Z are the same or different at each occurrence and are O, S, Se, N(H), or P(H). In certain instances, the present invention relates to the aforementioned polymer, where Ri is hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, olefin, silyl, alkylsilyl, arylsilyl, alkylaryl, or arylalkyl group.

In certain instances, the present invention relates to the aforementioned polymer, where Ri is hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, olefin, silyl, alkylsilyl, arylsilyl, alkylaryl, or arylalkyl group substituted internally or terminally by one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, or halogen substituents.

In certain instances, the present invention relates to the aforementioned polymer, where Ri is a polymer (such as poly(ethylene glycol), poly(ethylene oxide), or a poly(hydroxyacid)), a carbohydrate, a protein, a polypeptide, an amino acid, a nucleic acid, a nucleotide, a polynucleotide, any DNA or RNA segment, a lipid, a polysaccharide, an antibody, a pharmaceutical agent, or any epitope for a biological receptor.

In certain instances, the present invention relates to the aforementioned polymer, where Rj is a photocrosslinkable, chemically, or ionically crosslinkable group. In certain instances, the present invention relates to the aforementioned polymer, in which D is a straight or branched alkyl chain of about 1-5 carbons, m is 0 or 1, and R₂, R₃, R₄, R₅, R₆, and R₇ are the same or different at each occurrence and are hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, alkoxy, aryloxy, olefin, alkylamine, dialkylamine, arylamine, diarylamine, alkylamide, dialkylamide, arylamide, diarylamide, alkylaryl, or arylalkyl group.

In certain instances, the present invention relates to the aforementioned polymer comprised of repeating units of General Structure II, where L, N, and J are the same or different at each occurrence and are O, S, Se, N(H), or P(H). In certain instances, the present invention relates to the aforementioned polymer where Ri is hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, olefin, silyl, alkylsilyl, arylsilyl, alkylaryl, or arylalkyl group.

In certain instances, the present invention relates to the aforementioned polymer where Ri is hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, olefin, silyl, alkylsilyl, arylsilyl, alkylaryl, or arylalkyl group substituted internally or terminally by one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, or halogen substituents.

In certain instances, the present invention relates to the aforementioned polymer where Ri is a polymer selected from the group consisting of poly(ethylene glycols), poly(ethylene oxides), and poly(hydroxyacids, or is a carbohydrate, a protein, a polypeptide, an amino acid, a nucleic acid, a nucleotide, a polynucleotide, a DNA or RNA segment, a lipid, a polysaccharide, an antibody, a pharmaceutical agent, or an epitope for a biological receptor. In certain instances, the present invention relates to the aforementioned polymer where Ri is a photocrosslinkable, chemically, or ionically crosslinkable group.

In certain instances, the present invention relates to the aforementioned polymer, where D is a straight or branched alkyl chain of about 1-5 carbons, q and r are the same or different at each occurrence and are 0 or 1, and R₇, R₈, R₉, R₁₀, Rn, Ri₂, R₁₃, and Ri₄ are the same or different at each occurrence and are hydrogen, a straight or branched alkyl chain of about 1-20 carbons, cycloalkyl, aryl, alkoxy, aryloxy, olefin, alkylamine, dialkylamine, arylamine, diarylamine, alkylamide, dialkylamide, arylamide, diarylamide, alkylaryl, or arylalkyl group.

In certain instances, the present invention relates to the aforementioned block or random copolymer comprised of repeating units of general Structure III, where M, T, and Q are the same or different at each occurrence and are O, S, Se, N(H), or P(H), e is 0 or 1-9, and Ri₅ is a straight or branched alkyl chain of about 1-5 carbons, unsubstituted or substituted with one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, or halogen substituents In certain instances, the present invention relates to the aforementioned block or random copolymer comprised of repeating units of general Structure III, where M, T, and Q are the same or different at each occurrence and are O, S, Se, N(H), or P(H), and R₁₅ is a straight or branched alkyl chain of about 1-5 carbons, unsubstituted or substituted with one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, or halogen substituents.

In certain instances, the present invention relates to the aforementioned block or random copolymer comprised of repeating units of general Structure III, where M, T, and Q are the same or different at each occurrence and are O, S, Se, N(H), or P(H), and Rl 5 is a straight or branched alkyl chain of about 1-5 carbons, unsubstituted or substituted with one or more hydroxyl, hydroxyether, carboxyl, carboxyester, carboxyamide, amino, mono- or di-substituted amino, thiol, thioester, sulfate, phosphate, phosphonate, or halogen substituents.

Another aspect of the present invention relates to a higher order block or random copolymer comprised of three or more different repeating units, and having one or more repeating units described above, such as a polyglyerol glycine carbonate-polyglycerol succinic acid copolymer.

Another aspect of the present invention relates to a block or random copolymer as described above, which includes at least one terminal crosslinkable group selected from the group consisting of amines, thiols, amides, phosphates, sulphates, hydroxides, alkenes, and alkynes. In certain instances, the present invention relates to the aforementioned block or random copolymer where X, Y, M is O, S, N-H, N-R, and wherein R is -H, CH₂, CR₂, Se or an isoelectronic species of oxygen.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein an amino acid(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein a polypeptide(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein an antibody(ies) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z. In certain instances, the present invention relates to the aforementioned block or random copolymer wherein a nucleotide(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein a nucleoside(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein an oligonucleotide(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned block or random copolymer wherein a ligand(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z that binds to a biological receptor. In certain instances, the present invention relates to the aforementioned block or random copolymer wherein a pharmaceutical agent(s) is attached to R₁, R₂, R₃, R₄, R₅, A, and/or Z.

In certain instances, the present invention relates to the aforementioned crosslinkable or noncrosslinkable polymer or copolymer wherein the polymer is a dendritic macromolecule including at least one polymer selected from the group consisting of dendrimers, hybrid linear-dendrimers, dendrons, or hyperbranched polymers according to one of the general formulas or such similar structures below, where R₃, R₄, which may be the same or different, are a repeat pattern of B, and n is about 0 to 50.

etc

In certain instances, the present invention relates to the aforementioned polymer, wherein X, Y, M is O, S, N-H, N-R, wherein R is -H, CH₂, CR₂ or a chain as defined above, Se or any isoelectronic species of oxygen

In certain instances, the present invention relates to the aforementioned polymer, wherein X, Y, M is O, S, N-H, N-R, wherein R is -H, CH₂, CR₂ or a chain as defined above, Se or any isoelectronic species of oxygen.

In certain instances, the present invention relates to the aforementioned polymer where R₃ and R₄ are carboxylic acid with a protecting group such as but not limited to a phthalimidomethyl ester, a t-butyldimethylsilyl ester, or a t-butyldiphenylsilyl ester.

In certain instances, the present invention relates to the aforementioned polymer where R₃, R₄, A, and Z are the same or different, R₃ and R₄ are repeated a certain number of times, and terminate in -H, -OH, -CH₃, carboxylic acid, sulfate, phosphate, aldehyde, activated ester, methoxy, amine, amide, thiol, disulfide, straight or branched chain alkane, straight or branched chain alkene, straight or branched chain ester, straight or branched chain ether, straight or branched chain silane, straight or branched chain urethane, straight or branched chain, carbonate, straight or branched chain sulfate, straight or branched chain phosphate, straight or branched chain thiol urethane, straight or branched chain amine, straight or branched chain thiol urea, straight or branched chain thiol ether, straight or branched chain thiol ester, or any combination thereof, and wherein c is a natural or unnatural amino acid.

In certain instances, the present invention relates to the aforementioned polymer having a straight or branched chain of 1-50 carbon atoms and wherein the chain is fully saturated, fully unsaturated or any combination therein.

In certain instances, the present invention relates to the aforementioned polymer wherein straight or branched chains are the same number of carbons or different and wherein R₃, R₄, A, Z are any combination of linkers selected from the group consisting of esters, silanes, ureas, amides, amines, urethanes, thiol-urethanes, carbonates, carbamates, thio-ethers, thio-esters, sulfates, phosphates and ethers.

In certain instances, the present invention relates to the aforementioned polymer wherein chains include at least one selected from hydrocarbons, flourocarbons, halocarbons, alkenes, and alkynes.

In certain instances, the present invention relates to the aforementioned polymer wherein said chains include polyethers, polyesters, poly amines, polyacrylic acids, polyamino acids, polynucleic acids and polysaccharides of molecular weight ranging from

200-1,000,000, and wherein said chain contains 1 or more crosslinkable or photopolymerizable group.

In certain instances, the present invention relates to the aforementioned polymer wherein the chains include at least one of PEG, PLA, PGA, PGLA, and PMMA.

In certain instances, the present invention relates to the aforementioned block or random copolymer, which includes at least one terminal crosslinkable or photopolymerizable group selected from the group consisting of amines, thiols, amides, phosphates, sulphates, hydroxides, alkenes, activated esters, malemides, aldehydes, and alkynes.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with amino acid(s), such as cysteine, attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with polypeptide(s) attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with an antibody(ies) or single chain antibody(ies) attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with a nucleotide(s) attached to Z, A, R₃, and/or R₄..

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with a nucleoside(s) attached to Z₃ A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with oligonucleotide(s) attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with ligand(s) attached to Z, A, R₃, and/or R₄ that binds to a biological receptor.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with a pharmaceutical agent(s) attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with a pharmaceutical agent attached to Z, A, R₃, and/or R₄ and is at least one selected from the group consisting of antibacterial, anticancer, anti-inflammatory, and antiviral.

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times to produce a polymer in which a pharmaceutical agent(s) is encapsulated or chemically bound to the polymer.

In certain instances, the present invention relates to the aforementioned polymer wherein camptothecin or a deriviative of campothethcin is encapsulated

In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with a carbohydrate(s) attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein R₃ and R₄ are repeated a certain number of times and terminates with the carbohydrate mannose or sialic acid attached to the polymer.

In certain instances, the present invention relates to the aforementioned polymer which includes a polymer or copolymer of a polyester, polyamide, polyether, or polycarbonate at the center or periphery of the polymers above taken from the structures below.

Structure I

Structure II

Structure III

In certain instances, the present invention relates to the aforementioned polymer block or random copolymer which includes at least one terminal or internal crosslinkable group selected from the group consisting of amines, thiols, amides, phosphates, sulphates, hydroxides, alkenes, and alkynes. In certain instances, the present invention relates to the aforementioned polymer wherein X, Y, M is O, S, N-H, N-R, wherein R is -H, CH₂, CR₂ or a chain as defined above, Se or any isoelectronic species of oxygen.

In certain instances, the present invention relates to the aforementioned polymer wherein an amino acid(s) is attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein a polypeptide(s) is attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein an antibody(ies) or single chain antibody(ies) is attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein a nucleotide(s) is attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein a nucleoside(s) is attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein an oligonucleotide(s) is attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein a ligand(s) is attached to Z₅ A, R₃, and/or R₄ that binds to a biological receptor.

In certain instances, the present invention relates to the aforementioned polymer wherein a pharmaceutical agent(s) is attached to Z, A, R₃, and/or R₄.

In certain instances, the present invention relates to the aforementioned polymer wherein a carbohydrate(s) is attached to Z, A, R₃, and/or R₄. In certain instances, the present invention relates to the aforementioned polymer wherein a pharmaceutical agent(s) is attached to Z, A, R₃, and/or R₄ and is at least one selected from the group consisting of antibacterial, anticancer, anti-inflammatory, and antiviral.

In certain instances, the present invention relates to the aforementioned polymer wherein the carbohydrate is mannose or sialic acid is covalently attached to the polymer.

Another aspect of the present invention relates to a surgical procedure which comprises using a photopolymerizable, or chemically crosslinkable, or non-covalently crosslinkable dendritic polymer or copolymer.

In certain instances, the present invention relates to the dendritic polymer or copolymer which optionally contains at least one stereochemical center.

In certain instances, the present invention relates to the dendritic polymer or copolymer which is of D or L configuration.

In certain instances, the present invention relates to the dendritic polymer or copolymer wherein the final dendritic polymer or monomer is chiral or is achiral. In certain instances, the present invention relates to the dendritic polymer or copolymer which contains at least one site where the branching is incomplete.

In certain instances, the present invention relates to a crosslinkable/photocrosslinkable/reactionary dendritic polymer or copolymer which contains at least one site where the branching is incomplete.

In certain instances, the present invention relates to a crosslinkable/photocrosslinkable/reactionary dendritic polymer or copolymer which contains at least one site where the branching is incomplete which forms a hydrogel.

In certain instances, the present invention relates to a crosslinkable/photocrosslinkable/reactionary dendritic polymer or copolymer which contains at least one site where the branching is incomplete and used for drug delivery.

In certain instances, the present invention relates to a crosslinkable/photocrosslinkable/reactionary dendritic polymer or copolymer which contains at least one site where the branching is incomplete and used as a lens. In certain instances, the present invention relates to a dendritic polymer or copolymer made by a convergent or divergent synthesis.

In certain instances, the dendritic polymer of the invention relates to

One aspect of the present invention relates to using dendritic polymeric gels and hydrogels that contain nanoparticles for ophthalmic lens applications. Simple polymer gels (including hydrogels) are 3D polymeric materials that exhibit the ability to swell in water and to retain a fraction of water within the structure without dissolving. The physical properties exhibited by gels, such as water content, sensitivity to environmental conditions {e.g., pH, temperature, solvent, and stress), soft, adhesivity, and rubbery consistency are favorable for biomedical and biotechnological applications. Indeed, gels may be used as coatings (e.g., biosensors, catheters, and sutures), as "homogeneous" materials (e.g., contact lenses, burn dressings, and dentures), and as devices (e.g., artificial organs and drug delivery systems) (Peppas, N. A. Hydrogel in Medicine and Pharmacy, VoI I and II 1987 ^'. Wichterle, O.; Lim, D. Nature 1960, 185, 117-118. Ottenbrite, R. M.; Huang, S. J.; Park, K. Hydrogels and Biodegradable polymers for Bioapplications 1994; Vol. 627, pp 268). In certain instances, crosslinkable nanoparticles are used with crosslinkable polymers to form transparent hydrogels.

Nanoparticles

Nanoparticles are particles that generally have a diameter of less than about 500 nm. Many nanoparticles exhibit interesting properties, e.g., high refractive index, due to their size and composition. It has been reported that nanoparticles added to an optically clear plastic cause an increase in the refractive index of the plastic, and thus are useful for optical applications (Naussbaumer, Rene J. et al "Polymer-TiC>2 Nanocomposites: A Route Towards Visually Transparent Broadband UV Filters and High Refractive Index Materials" Marcomol. Mater. Eng. 2003, 288, No.l). Likewise, nanoparticles (i.e., iron nanoparticles) dispersed in a hydrogel at pH 7 exhibit magnetic properties. V. Cabuil et al. in "Magnetic Nanoparticles Trapped in pH 7 Hydrogels as a Tool to Characterize the Properties of the Polymeric Network" (Adv. Mater. 2000, 12, No. 6 416-417). Notably, Cabuil's nanoparticle-hydrogel composite is not useful for lens applications because it is not transparent.

A large variety of nanoparticle compositions are amenable to the present invention. Representative examples of nanoparticle compositions include various metals, metal oxides, sulfides, zeolites, silica, ceramic, or combinations thereof. In certain instances, the nanoparticles are made of titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxides, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, or ceramic. In certain instances, the nanoparticles are carbon-based nanoparticles. The nanoparictles of the invention may also be a composite of one or more metal oxides or sulfides.

Many different types of small particles (nanoparticles or micron-sized particles) are commercially available from various manufacturers including: Bangs Laboratories (Fishers, Ind.); Promega (Madison, Wis.); Dynal Inc.(Lake Success, N. Y.); Advanced Magnetics Inc. (Surrey, U.K.); CPG Inc. (Lincoln Park, N.J.); Cortex Biochem (San Leandro, Calif.); European Institute of Science (Lund, Sweden); Ferrofluidics Corp. (Nashua, N.H.); FeRx Inc.; (San Diego, Calif.); Immunicon Corp.; (Huntingdon Valley, Pa.); Magnetically Delivered Therapeutics Inc. (San Diego, Calif.); Miltenyi Biotec GmbH (USA); Microcaps GmbH (Rostock, Germany); PolyMicrospheres Inc. (Indianapolis, Ind.); Scigen Ltd. (Kent, U.K.); Seradyn Inc.; (Indianapolis, Ind.); and Spherotech Inc. (Libertyville, 111.). Many of these particles are made using conventional techniques, such as grinding and milling, emulsion polymerization, block copolymerization, and microemulsion. Nanoparticles can also be manufactured by a gas condensation process, such as that described in U.S. Pat. Nos. 5,128,081 and 5,320,800, the contents of which are incorporated herein by reference. A gas condensation process for the preparation of nanoparticles typically involves evaporation of a metal precursor material from which the nanoparticles will be synthesized at gas pressures of less than one or equal to one atmosphere. The evaporated metal condenses into small particles in the gas atmosphere and the resulting nanoparticles are collected on a surface within the reactor. Any metal or metal compound capable of being volatilized may be used to form the nanoparticles for use in the present invention. Exemplary metals are titanium, copper, silver, gold, platinum, and palladium. The metal nanoparticles may be further subjected to a reactive gas atmosphere to form oxides, nitrides, carbides, sulfides, fluorides, and chlorides. Exemplary metal oxide nanoparticles are those composed of aluminum oxide, antimony tin oxide, cerium oxide, copper oxide, indium oxide, indium tin oxide, iron oxide, silicon dioxide, tin oxide, titanium dioxide, yttrium oxide, zinc oxide, barium oxide, calcium oxide, chromium oxide, magnesium oxide, manganese oxide, molybdenum oxide, neodymium oxide, and strontium oxide. Metal titanate and metal silicate nanoparticles including, for example, strontium titanate, barium titanate, barium strontium titanate, and zirconium silicate may also be used. Titanium dioxide nanoparticles are preferred for use as polymer fillers. Titanium dioxide nanoparticles of varying particle size, synthesized by a gas condensation process, are commercially available from Nanophase Technologies Corporation. Nanophase Technologies also manufactures the metal, metal oxide, metal titanate and metal silicate nanoparticles listed above.

Nanoparticles of various sizes are amenable to the present invention. In certain instances, the nanoparticles have a diameter of about 0.1 nm to about 200 nm. In certain instances, the nanoparticles have a diameter of about 0.1 nm to about 100 nm. In certain instances, the nanoparticles have a diameter of about 0.1 nm to about 50 nm. In certain instances, the nanoparticles have a diameter of about 0.1 nm to about 25 nm. In certain instances, nanoparticles have a diameter less than about 50 nm. In certain instances, nanoparticles have a diameter less than about 20 nm. Another aspect of the invention relates to hybrid organic-metal oxide, organic-metal sulfoxide, or organic-ceramic nanoparticles. Nanoparticles may be modified with small molecules or polymers via covalent or non-covalent interactions (e.g., electrostatics) to improve their properties for an ophthalmic use. For example, these organic-coated nanoparticles can improve stability, optical clarity, and improve dispersion in a polymer matrix. In addition, nanoparticles can improve anti-microbial properties, cross-linking, modulus, viscosity, swelling properties, adhesion to capsular bag, and specific wavelength absorption. Also, if the nanoparticle contains titanium dioxide or zinc oxide, this will absorb harmful UV light and act as an antibacterial agent or anti-proliferative agent. Methods for the preparation of hybrid organic-inorganic nanoparticles and inorganic/ceramic nanoparticles are described herein.

It has been reported that TiO₂ has low surface potential (< 20 mv) between pH 5.5 to 7.5, and ZnO has a low surface potential between pH 7.5 and 10. See Diebold et. al. in J. Coatings Tech. 2003, 75, 942. The low surface potential corresponds to relatively neutral particles. The low surface potential does not allow for charge-charge repulsion of the individual particles, and thus leads to aggregation in aqueous solutions. The low surface- potential near biological pH is generally true for unmodified inorganic nanoparticles. To overcome the particle aggregation it is important to design nanoparticles that are thermodynamically stable near the pH of the biological system. This can be accomplished in a number of ways.

Mori et al. has demonstrated that organically modified silica materials can be prepared via acid condensation of a speciality alkyltrialkoxysilane (J. Am. Chem. Soc. 2003, 125, 3712). This silica is claimed to be optically transparent at or near pH 7. In this case, each silicon atom will have an organic substituent attached to it, and therefore the silica network incorporates organic functional groups. However, there is some uncertainty how this will impact the refractive index of the molecules.

The present application describes surface modification of nanoparticles by either post- reaction of the nanoparticles with organic groups or in situ surface-modification during particle formation. The former entails reaction of alkyltrialkoxysilanes, dialkyldialkoxysilanes, trialkylalkoxysilanes, alkylchlorosilanes, dialkyldichlorosilanes, or trialkylchlorosilanes with the surface of inorganic particles. In certain instances, the inorganic particles are less than about 10 nm in diameter. The alkyl group consists of an alkyl space between the silicon and an organic functional group. In certain instances, the alkyl group is substituted with a functional group. Representative functional groups include amino, vinyl, allyl, acrylate, methacrylate, alkanolamine, sulfate, carboxylic acid, hydroxyl, polyethylene glycol, polypropylene glycol, polyvinyl alcohol, epoxide, aldehyde, ketone, 1,3-diketone, amide, ester, and polar cylic organic moieties, such as imidazoles and pyrolidinones, and ureido. These organic functional groups can be used as is or further modified to create a charged surface at the pH of a biological system.

In situ surface modification during particle formation occurs by addition of the above reactive molecules during the particle formation. The derivatized silanes are placed in the aqueous phase to form micelles or nucleation sites for the particle formation. TiCl₄, tetralkoxytitanium, or tetralkoxysilane is then added to the solution and hydrolyzed to create a nanoparticle with a preformed surface. This could be accomplished in an inverse phase process. For example, alkyltrialkoxysilane or alkylSi(OH)₃ could be added to a high boiling alkane (octane or dodecane). This would form inverse micelles with the polar groups on the interior of the micelles. TiCl₄ or SiCl₄ would migrate to the micelles during a controlled hydrolysis (under reflux, the HCl would leave the system since it would not be soluble in the organic phase).

Another approach is to modify the surface through the use of chelating organic molecules. It is well known that increased stability can be obtained in otherwise reactive molecules. For example, simple titanium alkoxylates, such as tetramethoxytitanium, readily undergoe hydrolysis in the presence of trace water, while the addition of chelating groups, such as acetylacetonate, triethanolamine, or lactate, greatly reduce the rate of hydrolysis. Another aspect of the invention relates to the fixation of organic chelates to the surface of inorganic particles. The organic chelates contain groups that will be charged at the pH of a biological system. One example is complexation of lactate to the surface of a titanium particle. The complexation occurs through a covalent bond between the alcohol and titanium and donation of the electrons from the C=O of the acid. The acid exists as the salt, ammonium or sodium, at elevated pH (>5). This gives the desired surface charge at pH 7.

Another approach is the encapsulation of nanoparticles into a latex particle of nanometer size. This technique offers a novel method of stabilizing nanoparticles. Radical induced polymerization of reactive monomers, such as methylmethacrylate, butyl acrylate, acrylic acid, methacrylic acid, styrene, or vinyl acetate, can be conducted over a wide range of pH values. Encapsulating an inorganic particle has been reported. For example, El-Aaser et al. (J. Poly. ScL Part A: Poly. Chem. 2000, 38, 4441) provide examples and references for TiO₂ encapsulation. Typical particles that have been examined range in the size of 20-200 nm. However, in the present invention, polymer (e.g., latex) encapsulated inorganic particles that are <20 nm can be formed using emulsion polymerization techniques, including batch, semi- batch, mini, and micro emulsion techniques. In this size range, complete encapsulation may be obtained. However, it is only necessary that the particles are sufficiently encapsulated to prevent aggregation upon a change in pH. During the encapsulation, the particle size will grow and possibly begin to refract light. To retain optical clarity, the organic layer may be made to swell such that the organic phase becomes a gel with the particle locked in the gel. In addition, polymerizable groups can be prefixed to the surface of the particles. These reactive sites will allow for complete coverage of the surface of the particle. Well known techniques, such as chain transfer reagents, can be used to regulate the polymer chain length attached to the polymer. In addition, the water solubility can be modified by varying the abundance of acid functionalitites in the polymer. Notably, the polymer properties may also be modified using diacrylates spaced by PEG. The nanoparticles can be further modified so that they are covalently linked to a polymer in the hydrogel. For example, the nanoparticle can be modified to include a nucleophile on the surface of the nanoparticle. The nucleophile-active nanoparticle is then combined with the polymers for formation of the hydrogel composite. The nucleophile- active nanoparticle would couple to the one or more of the electrophilic groups on the polymer and become crosslinked with the hydrogel. For example, Mori's nanoparticles contain free alcohols on the surface. These may be converted to a N-terminal cysteine moiety in a dendritic fashion to provide a thiol group for crosslinking. Representative examples of nucleophilic functional groups amenable to the present invention include thiol, amino, hydroxyl, and the like. The opposite reactivity system, an electrophile-active nanoparticle, is also possible. Representative examples of electrophilic functional groups include aldehydes, activated esters, acrylates, and the like. Another aspect of the invetion relates to nanoparticles containing olefins, alkenes, or alkynes which can be crosslinked within the hydrogel. These types of functional groups can be crosslinked using photochemistry or a radical initiator. Nanoparticles can also be suspended in aqueous, saline, ionic, supercritical gas (such as liquid carbon dioxide) or organic solvents to aid in the dispersion within the polymer lens during lens formation, such as in the formation of a contact lens or intraocular lens (IOL). The lens formation process can be performed in vivo, in vitro, or ex vivo. Importantly, the nanoparticle suspension does not degrade the optical transmission properties to the extent that the lens becomes unsuitable for use in the human eye. Rather, the nanoparticle suspension may improve certain characteristics, such as refractive index, clarity, specific wavelength absorption, or modulus of the material. The nanoparticle-lens composites can be also used to prepare a gradient refractive-index lens for ocular use, where different regions or zones of the lens contains different concentrations of nanoparticles, and thus a different refractive index. The use of nanoparticles may be used to manipulate characteristics of the replacement lens such that errors present in the original lens are corrected or improved upon. For instance, manipulation of the polymer's refractive index can enable correction of spherical refractive errors. [Ho₅2001 #10]

The refractive index can also be changed or tuned, independently of changing other properties, such as modulus, and polymeric make-up. The ability to independently modify the refractive index is highly desirable because it simplifies the formulation process. Removing the link between polymer content and refractive index also allows the design of a weak, low polymer-content gel. For example, the refractive index of a solution can be varied from 1.33 to more than 1.42 by increasing the weight percent to greater than 12 w/t%. Importantly, the viscosity of these solution changes only minimally (1 to 6 cps).

Crosslinked Gels or Networks

To prepare the transparent dendritic crosslinked gel/network of the present invention, dendrimers or dendritic polymers are crosslinked using either light or a chemical crosslinking reaction in the presence of nanoparticles. A further embodiment of this invention is the crosslinking between a first dendritic polymer and and second dendritic polymer or between a dendritic polymer and a linear polymer. The crosslinking event produces a gel or network in the presence of nanoparticles. An additional embodiment of this invention is the crosslinking between dendritic polymers, linear polymers, and nanoparticles or any combination thereof to form a crosslinked gel or network to form a transparent hydrogel lens. The gels can be highly hydrated and hydrophilic. The crosslinked networks are useful as lens replacement materials, lens substitute materials, corneal inlays, and intraocular lenses. In certain aspects of the invention, the nanoparticles are present in about 1 to about 40 weight percent. The weight percent is calculated by dividing the cumulative weight of the nanoparticles by the total weight of the hydrogel composition. In certain instances, the nanoparticles are present in about 1 to about 30 weight percent or in about 1 to about 20 weight percent. In certain instances, the nanoparticles are present in about 1 to about 10 weight percent or in about 1 to about 5 weight percent. In certain instances, the nanoparticles are present in about 5 to about 25 weight percent. Alternatively, the nanoparticles are present in about 15 to about 40 weight percent.

In instances where the crosslinking is not activated by light, the polymers and/or nanoparticles contain functional groups that will react with each other to form the gel. In certain instances, the dendritic polymers have more than two nucleophilic functional groups, such as primary amino (-NH₂) or thiol (-SH) groups, which can react with electrophilic groups. In certain instances, the electrophilic group is an acrylate, aldehyde, or activated ester. In certain instances, each functional group on a multifunctionally dendritic polymer is capable of covalently binding with another polymer. Formation of a covlant linkage between the dendrimers creates the hydrogel network.

Covalently crosslinked networks can be formed by reacting an activated ester (such as an N-hydroxysuccinimide) with an amine or thiol (such as a terminal primary or secondary amine, lys, cys, etc.). Thiol- or cysteine-terminated dendritic structures that form a disulfide crosslinked network with another thiol- or cysteine-terminated dendritic or linear polymer will also form a gel. In addition, gels may be formed by reaction of an aldehyde- functionalized small molecule or polymer and an amine- or cysteine- functionalized polymer. An alternative method is to have a maleimide- or vinylsulfone-functionalized dendritic polymer react with a thiol-functionalized dendritic, linear, comb, or other polymer to form the gel. A functionalized succinimidyl glutarate dendritic polymer with an acid- terminated dendritic, linear, comb, or other polymer can also be used to from a gel. An acrylate-functionalized polymer reacts with an amine- or thiol-functionalized polymer to form the crosslinked gel. A further embodiment of this invention is the use of a chemical peptide ligation reaction to create a crosslinked gel involving a dendritic polymer. In this reaction an aldehyde or aldehyde-acid reacts with a cysteine functionalized polymer to form a gel or crosslinked network.

Another aspect of the present invention relates to dendritic or branched polymers or copolymers composed of monomers synthesized by combining branching compounds with other linear or branched building blocks. Both components are biocompatible or are natural metabolites in vivo such as glycerol, citric acid, lactic acid, glycolic acid, adipic acid, caproic acid, ribose, glucose, succinic acid, malic acid, amino acids, peptides, synthetic peptide analogs, or poly(ethylene glycol). In certain instances, one of the monomers is a branched structure, such as glycerol, combined with one of the other components. In certain instances, the present invention relates to polymers and/or nanoparticles derivatized with peripheral compounds possessing an olefin such as acrylate or methacrylate.

In certain instances, the present invention relates to the aforementioned polymers and/or nanoparticles derivatized with peripheral compounds such as cysteine, lysine, other amino acids, or any other compounds that would provide terminal nucleophiles (such as amines, thiols, or hydroxyl groups) or electrophiles (such as NHS esters, maleimides, aldehydes, or ketones). In certain instances, the present invention relates to the forementioned polymers and/or nanoparticles for subsequent polymerization/crosslinking/reaction with another linear or branched structure with either olefmic, electrophilic or nucleophilic groups, respectively to form a gel. In certain instances, the present invention relates to the aforementioned polymers and/or nanoparticles for subsequent polymerization/crosslinking/reaction with another linear or branched structure via a photopolymerization process (single or multi-photon process) to form a gel.

Another aspect of the present invention relates to a branching structure with at least three functional groups comprising glycerol, citric acid, malic acid, amino acids, peptides, synthetic peptide analogs, or other dendritic strucutures synthesized to produce terminal olefins, such as acrylate or methacrylate groups; nucleophiles such as amines, thiols, hydroxyl groups; or electrophiles, such as NHS esters, maleimides, aldehydes, or ketones for subsequent polymerization/crosslinking with another linear or branched structure with either olefinic, electrophilic or nucleophilic groups, respectively in the presence of functionalized or nonfunctionalized nanoparticles.

Another aspect of the present invention relates to a branching structure with at least three functional groups, such as glycerol, citric acid, malic acid, amino acids, peptides, synthetic peptide analogs, or other dendritic structures derivatized with peripheral compounds including, but not limited to, cysteine, lysine, other amino acids, or any other compounds that would provide terminal olefins (such as acrylate or methacrylate groups), nucleophiles (such as amines, thiols, and hydroxyl groups) or electrophiles (such as NHS esters, maleimides, aldehydes, and ketones) for subsequent polymerization/crosslinking with another linear or branched structure with either olefinic, electrophilic, or nucleophilic groups, respectively in the presence of nanoparticles.

Another aspect of the present invention relates to a branching structure composed of three lysine amino acids with four cysteine amino acids on the periphery with the structure CysLys(Cys)Lys(CysLys(Cys))OMe*4HCl as described in the examples. In certain instances, the present invention relates to a branching structure composed of three lysine amino acids with peripheral amines on the periphery with the structure

(Lys)Lys(Lys)OMe^#4HCl as described in the examples. In certain instances, the present invention relates to the aforementioned polymers for subsequent polymerization/crosslinking/reaction with another linear or branched structure with olefinic, electrophilic, or nucleophilic groups to form a gel.

Another aspect of the invention relates to the aforementioned polymer containing poly(ethylene glycol). In certain instances, the poly(ethylene glycol) has a number average molecular weight of about 200 g/mol to about 200,000 g/mol. In certain instances, the poly(ethylene glycol) has at least two electrophilic groups. In certain instances, the poly(ethylene glycol) has at least two nucleophilic groups. In certain instances, the poly(ethylene glycol) has a number average molecular weight of about 200 g/mol to about 200,000 g/mol and is functionalized with an olefin, aldehyde, maleimide, or NHS ester.

The hydrogels of the present invention can be prepared by combining solutions containing the components described above, e.g., the nanoparticle and dendrimer. The components may be dissolved or suspended in an aqueous solution. The aqueous solution can be water, buffered aqueous media, saline, buffered saline, solutions of amino acids, solutions of sugars, solutions of vitamins, solutions of carbohydrates or combinations of any two or more thereof. In certain instances, the components used to prepare the hydrogel are contained in a delivery device that physically separates the components until the components are mixed by the end user. The delivery device may be a dual-barrel syringe with a mixing device.

Another aspect of the present invention relates to packaging of the polymerizable dendrimeric compounds in an aqueous solution at a preselected pH and molarity. A poly(ethylene glycol) having a number average molecular weight of about 200 g/mol to about 200,000 g/mol with at least two electrophilic or nucleophilic groups is contained in another aqueous solution at a preselected pH and molarity. When mixture containing the dendrimeric compound and PEG are combined, the pH and molarities of the two solutions produce a final desired solution with a different pH.

Another aspect of the present invention relates to a method of using the polymers, branching structures, and their hydrogels as a drug delivery vehicle and an adhesive/sealant to aid in the repair or sealing of an ophthalmic wound. Another aspect of the present invention relates to a method of using the polymers, branching structures, nanoparticles and their hydrogels for ophthalmic procedure wherein the drug has properties such as antimicrobial, antibacterial, anti-inflamatory, etc.

Another aspect of the present invention relates to a method of using a crosslinkable/polymerizable/reactionary dendritic polymers, branching structures, and their hydrogels as a drug delivery vehicle and an adhesive/sealant to aid in the repair or sealing of an ophthalmic wound wherein the drug has antimicrobial or antibacterial properties.

Another aspect of the present invention relates to a method of using a crosslinkable/polymerizable/reactionary coating on the nanoparticle such that the nanoparticle is covalently bound to the hydrogel network. This coating can contain one or more of the same or different electrophile or nucloephile such that the nanoparticles will react with dendritic and/or linear polymers that constitute the hydrogel.

Another aspect of the present invention relates to a crosslinkable/polymerizable/reactionary nanoparticle, dendritic polymer or monomer wherein the crosslinking is of covalent, ionic, electrostatic, and/or hydrophobic nature.

Another aspect of the present invention relates to a crosslinkable dendritic polymer, linear polymer, monomer, or nanoparticle wherein the crosslinking reaction involves a nucleophile and electrophile.

Another aspect of the present invention relates to a crosslinkable dendritic polymer, linear polymer, monomer, or nanoparticle wherein the crosslinking reaction is a peptide ligation reaction. Another aspect of the present invention relates to a crosslinkable dendritic polymer, linear polymer, monomer, or nanoparticle wherein the crosslinking reaction is a

Diels-Alder reaction. Another aspect of the present invention relates to a crosslinkable dendritic polymer, linear polymer, monomer, or nanoparticle wherein the crosslinking reaction is a Michael Addition reaction.

Another aspect of the present invention relates to a crosslinkable crosslinkable dendritic polymer, linear polymer, monomer, or nanoparticle wherein the crosslinking reaction is a photochemical reaction using a UV or vis photoinitiator chromophore. Another aspect of the present invention relates to a crosslinkable branched or dendritic polymer in combination with a linear, comb, multi-block, star polymer(s), dendritic polymer and a nanoparticle as a lens material. Another aspect of the present invention relates to a method of using a crosslinkable branched or dendritic polymer combined with a crosslinkable small molecule(s) having a molecular weight less than about 1000 daltons for a medical or tissue engineering application.

Another aspect of the present invention relates to a crosslinkable branched or dendritic polymer or monomer, wherein the crosslinking dendritic polymer is combined with one or more linear, comb, multi-block, star polymers or crosslinkable comb, multi- block, star polymers. Another aspect of the present invention relates to a crosslinkable dendritic polymer or monomer wherein the final polymeric form is a gel or sheet. Another aspect of the present invention relates to the aforementioned polymers, branching structures, and their resulting hydrogels wherein the polymer or crosslinkable monomer is D or L configuration or a mixture. Another aspect of the present invention relates to the aforementioned polymers, branching structures, and their resulting hydrogels wherein the branching structure, linkages and or the incorporation of aromatic or hterocyclic groups changes the refractive index.

The hydrogels of the invention may also comprise an ingredient that absorbs ultraviolate light. A large number of materials are known to absorb ultra-violate light and are amenable to the present invention. Representative examples of materials that absorb ultra-violate light include titanium dioxide, zinc oxide, octocrylene, octdyl slicylate, homosalate, octyl methoxycinnamate, avobenzone-Parson 1789, cinoxate, ethylhexyl p- methoxycinnamate, oxybenzone, and benzophenone-3. In certain instances, the ingredient that absorbs ultraviolate light is titanium dioxide or zinc oxide. Sterilization Procedures

A variety of procedures are known in the art for sterilizing a chemical composition. Sterilization may be accomplished by chemical, physical, or irradiation techniques. Examples of chemical methods include exposure to ethylene oxide or hydrogen peroxide vapor. Examples of physical methods include sterilization by heat (dry or moist), retort canning, and filtration. The British Pharmacopoeia recommends heating at a minimum of 160 ⁰C for not less than 2 hours, a minimum of 170 ⁰C for not less than 1 hour and a minimum of 180 ⁰C for not less than 30 minutes for effective sterilization. For examples of heat sterilization, see U.S. Patent 6,136,326, which is hereby incorporated by reference. Passing the chemical composition through a membrane can be used to sterilize a composition. For example, the composition is filtered through a small pore filter such as a 0.22 micron filter which comprises material inert to the composition being filtered. In certain instances, the filtration is conducted in a Class 100,000 or better clean room. Examples of irradiation methods include gamma irradiation, electron beam irradiation, microwave irradiation, and irradiation using visible light. One preferred method is electron beam irradiation, as described in U.S. Patents 6,743,858; 6,248,800; and 6,143,805, each of which is hereby incorporated by reference.

There are several sources for electron beam irradiation. The two main groups of electron beam accelerators are: (1) a Dynamitron, which uses an insulated core transformer, and (2) radio frequency (RF) linear accelerators (linacs). The Dynamitron is a particle accelerator (4.5 MeV) designed to impart energy to electrons. The high energy electrons are generated and accelerated by the electrostatic fields of the accelerator electrodes arranged within the length of the glass-insulated beam tube (acceleration tube). These electrons, traveling through an extension of the evacuation beam tube and beam transport (drift pipe) are subjected to a magnet deflection system in order to produce a "scanned" beam, prior to leaving the vacuum enclosure through a beam window. The dose can be adjusted with the control of the percent scan, the beam current, and the conveyor speed. In certain instances, the electron-beam radiation employed may be maintained at an initial fluence of at least about 2 μCurie/cm², at least about 5 μCurie/cm², at least about 8 μCurie/cm², or at least about 10 μCurie/cm². In certain instances, the electron-beam radiation employed has an initial fluence of from about 2 to about 25 μCurie/cm². In certain instances, the electron- beam dosage is from about 5 to 50 kGray, or from about 15 to about 20 kGray with the specific dosage being selected relative to the density of material being subjected to electron- beam radiation as well as the amount of bioburden estimated to be therein. Such factors are well within the skill of the art.

The composition to be sterilized may be in any type of at least partially electron beam permeable container such as glass or plastic. In embodiments of the present invention, the container may be sealed or have an opening. Examples of glass containers include ampules, vials, syringes, pipettes, applicators, and the like. The penetration of electron beam irradiation is a function of the packaging. If there is not enough penetration from the side of a stationary electron beam, the container may be flipped or rotated to achieve adequate penetration. Alternatively, the electron beam source can be moved about a stationary package. In order to determine the dose distribution and dose penetration in product load, a dose map can be performed. This will identify the minimum and maximum dose zone within a product.

Procedures for sterilization using visible light are described in U.S. Patent 6,579,916, which is hereby incorporated by reference. The visible light for sterilization can be generated using any conventional generator of sufficient power and breadth of wavelength to effect sterilization. Generators are commercially available under the tradename PureBright® in-line sterilization systems from PurePulse Technologies, Inc. 4241 Ponderosa Ave, San Diego, Calif. 92123, USA. The PureBright® in-line sterilization system employs visible light to sterilize clear liquids at an intensity approximately 90000 times greater than surface sunlight. If the amount of UV light penetration is of concern, conventional UV absorbing materials can be used to filter out the UV light.

In a preferred embodiment, the composition is sterilized to provide a Sterility

Assurance Level (SAL) of at least about 10^"3. The Sterility Assurance Level measurement standard is described, for example, in ISO/CD 14937, the entire disclosure of which is incorporated herein by reference. In certain embodiments, the Sterility Assurance Level may be at least about 10^"4, at least about 10^"5, or at least about 10^"6.

Delivery Systems

The materials used to form the lens of the present invention may be delivered to a lens bag of a patient before the hydrogel forms. A large number of delivery systems are known in the art and are amenable to the present invention. In certain instances, a mixture comprising a polymerizable dendrimeric compound and nanoparticles is delivered to a lens bag of a patient. Alternatively, a first mixture comprising a polymerizable dendrimeric compound and nanoparticles is combined with a polymerization agent to form a second mixture, and the second mixture is delivered to the lens bag of a patient. In certain instances, the materials delivered to the lens bag have been sterilized. The delivery system may be a single-barrel syringe system. In certain instances, the single-barrel syringe is a double acting, single-barrel syringe system as displayed in Figure 12. In certazra szYwations, a double- or multi-barrel syringe system, as displayed in Figure 13, may be preferable. In instances where the polymerizable dendrimer is mixed with a polymerization agent prior to delivering the solution to the lens bag of a patient, a delivery device that flows two or more streams of liquid in a mixing chamber may be preferable. Alternatively, a delivery device that mixes two solids and two liquids and then separately flows these streams of liquid to a mixing chamber may be advantageous. In certain instances, a delivery system is used to deliver the lens-forming materials to the lens bag, wherein at least two dry, reactive components are stored together in a dry state and introduced into a liquid component(s) at the time of use to form a mixture that forms a hydrogel.

In certain instances, a sterilized hydrogel-nanoparticle composite is delivered to the lens bag using a syringe where the components of the hydrogel-nanoparticle composite are in liquid form, solid form, or a combination of solid and liquid forms prior to delivery.

Definitions

For convenience, certain terms employed in the specification, examples, and appended claims are collected here. The term "non-reversible hydrogel" refers to a hydrogel that does not undergo a transition between a gel and a solution state in response to temperature, pH, ionic strength, solvent composition, oxidative conditions sufficient to form a disulfide bond, or reducing conditions sufficient to reduce a disulfide bond. In certain instances, the non-reversible hydrogel comprises polymeric materials bonded together by C-C, C-N, C-O, and/or C-S covalent bonds.

The term "reversible hydrogel" refers to a hydrogel that undergoes a transition between a solution and a gel state in response to temperature, pH, ionic strength, solvent composition, oxidative conditions sufficient to form a disulfide bond, or reducing conditions sufficient to reduce a disulfide bond. In certain instances, the reversible hydrogel comprises polymeric materials bonded together by S-S covalent bonds.

The term "non-reversible polymer-nanoparticle composite" refers to a composition comprising a polymer and a nanoparticle that does not dissociate when subjected to reducing conditions sufficient to convert a disulfide moiety to thiols.

The term "nanoparticle" refers to a particle that has a diameter of less than about 500 nm. In certain instances, the nanoparticle has a diameter of about 0.1 nm to about 500 ran. In certain instances, the nanoparticle is made of a metal, metal oxide, metal sulfoxide, or ceramic. In certain instances, the nanoparticle is not made of protein.

The term "hybrid organic-inorganic nanoparticle" refers to a nanoparticle that has a core to which at least one organic compound is attached, wherein said core comprises a metal oxide, metal sulfoxide, or ceramic.

The term "silica coated nanoparticle" refers to a nanoparticle that has a core coated with silica or silica oxide, wherein said core comprises a metal, metal oxide, alkali metal oxide, metal sulfoxide or ceramic. In certain instances, an organic compound is attached to said nanoparticle.

The term "organic compound" refers to a compound having a molecular weight less than about 1500 g/mol and having at least about 90 weight percent C, H, N, or O atoms. In certain instances, the organic compound has a molecular weight less than about 750 g/mol. In certain instances, the organic compound has a molecular weight less than about 200 g/mol.

The term "generation" refers to the number of branched repeat units which emanate from the central core. For example a third generation (or G3) PGLSA dendrimer has three branching layers not including the core. The term "polymerize" as used herein refers to the process of converting a monomer to a chain of momomers, wherein the chain of momomers comprises at least about 5 monomers.

In certain instances, the chain of monomers comprises at least about 10 or 15 momomers.

In certain instances, the chain of monomers comprises at least about 25 or 40 momomers.

In certain instances, the chain of monomers comprises at least about 50 or 75 momomers. In certain instances, the chain of monomers comprises at least about 100 or 150 momomers. In instances wherein the monomelic unit has more than one functional group capable of forming a bond in the polymerization reaction, the term "polymerize" indicates that at least one of the functional groups capable of forming a bond in the polymerization reaction forms a bond with another compound, generally speaking, the other compound is another monomer. In certain instances, at least about 10% of the functional groups capable of forming a bond in a polymerization reaction form a bond to another monomer. In certain instances, at least about 25% of the functional groups capable of forming a bond in a polymerization reaction form a bond to another monomer. In certain instances, at least about 50% of the functional groups capable of forming a bond in a polymerization reaction form a bond to another monomer. In certain instances, at least about 75% of the functional groups capable of forming a bond in a polymerization reaction form a bond to another monomer. In certain instances, about 20% to about 50% of the functional groups capable of forming a bond in a polymerization reaction form a bond to another monomer. Furthermore, the term "polymerize" only requires that at least some of the monomer units in a given solution react to form a chain of monomers. In certain instances, about 10% to about 30% of the monomers react to form a chain of monomers. In certain instances, about 30% to about 50% of the monomers react to form a chain of monomers. In certain instances, about 50% to about 75% of the monomers react to form a chain of monomers. In certain instances, about 75% to about 85% of the monomers react to form a chain of monomers. In certain instances, about 85% to about 95% of the monomers react to form a chain of monomers. In certain instances, greater than about 95% of the monomers react to form a chain of monomers.

The term "Mw" as used herein refers to weight average molecular weight in g/mol.

The term "heteroatom" as used herein means an atom of any element other than carbon or hydrogen. Preferred heteroatoms are boron, nitrogen, oxygen, phosphorus, sulfur and selenium.

The term "alkyl" refers to the radical of saturated aliphatic groups, including straight-chain alkyl groups, branched-chain alkyl groups, cycloalkyl (alicyclic) groups, alkyl substituted cycloalkyl groups, and cycloalkyl substituted alkyl groups. In preferred embodiments, a straight chain or branched chain alkyl has 30 or fewer carbon atoms in its backbone (e.g., C1-C30 for straight chain, C3-C30 for branched chain), and more preferably 20 or fewer. Likewise, preferred cycloalkyls have from 3-10 carbon atoms in their ring structure, and more preferably have 5, 6 or 7 carbons in the ring structure.

Unless the number of carbons is otherwise specified, "lower alkyl" as used herein means an alkyl group, as defined above, but having from one to ten carbons, more preferably from one to six carbon atoms in its backbone structure. Likewise, "lower alkenyl" and "lower alkynyl" have similar chain lengths. Preferred alkyl groups are lower alkyls. In preferred embodiments, a substituent designated herein as alkyl is a lower alkyl.

The term "aralkyl", as used herein, refers to an alkyl group substituted with an aryl group (e.g., an aromatic or heteroaromatic group). The terms "alkenyl" and "alkynyl" refer to unsaturated aliphatic groups analogous in length and possible substitution to the alkyls described above, but that contain at least one double or triple bond respectively.

The term "aryl" as used herein includes 5-, 6- and 7-membered single-ring aromatic groups that may include from zero to four heteroatoms, for example, benzene, anthracene, naphthalene, pyrene, pyrrole, furan, thiophene, imidazole, oxazole, thiazole, triazole, pyrazole, pyridine, pyrazine, pyridazine and pyrimidine, and the like. Those aryl groups having heteroatoms in the ring structure may also be referred to as "aryl heterocycles" or "heteroaromatics." The aromatic ring can be substituted at one or more ring positions with such substituents as described above, for example, halogen, azide, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, alkoxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, sulfonamido, ketone, aldehyde, ester, heterocyclyl, aromatic or heteroaromatic moieties, -CF3, -CN, or the like.

The term "aryl" also includes polycyclic ring systems having two or more cyclic rings in which two or more carbons are common to two adjoining rings (the rings are "fused rings") wherein at least one of the rings is aromatic, e.g., the other cyclic rings can be cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls.

The terms ortho, meta and para apply to 1,2-, 1,3- and 1 ,4-disubstituted benzenes, respectively. For example, the names 1,2-dimethylbenzene and ørt/20-dimethylbenzene are synonymous. The terms "heterocyclyl" or "heterocyclic group" refer to 3- to 10-membered ring structures, more preferably 3- to 7-membered rings, whose ring structures include one to four heteroatoms. Heterocycles can also be polycycles. Heterocyclyl groups include, for example, thiophene, thianthrene, furan, pyran, isobenzofuran, chromene, xanthene, phenoxathiin, pyrrole, imidazole, pyrazole, isothiazole, isoxazole, pyridine, pyrazine, pyrimidine, pyridazine, indolizine, isoindole, indole, indazole, purine, quinolizine, isoquinoline, quinoline, phthalazine, naphthyridine, quinoxaline, quinazoline, cinnoline, pteridine, carbazole, carboline, phenanthridine, acridine, pyrimidine, phenanthroline, phenazine, phenarsazine, phenothiazine, furazan, phenoxazine, pyrrolidine, oxolane, thiolane, oxazole, piperidine, piperazine, morpholine, lactones, lactams such as azetidinones and pyrrolidinones, sultams, sultones, and the like. The heterocyclic ring can be substituted at one or more positions with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, -CF3, -CN, or the like.

The terms "polycyclyl" or "polycyclic group" refer to two or more rings (e.g., cycloalkyls, cycloalkenyls, cycloalkynyls, aryls and/or heterocyclyls) in which two or more carbons are common to two adjoining rings, e.g., the rings are "fused rings". Rings that are joined through non-adjacent atoms are termed "bridged" rings. Each of the rings of the polycycle can be substituted with such substituents as described above, as for example, halogen, alkyl, aralkyl, alkenyl, alkynyl, cycloalkyl, hydroxyl, amino, nitro, sulfhydryl, imino, amido, phosphonate, phosphinate, carbonyl, carboxyl, silyl, ether, alkylthio, sulfonyl, ketone, aldehyde, ester, a heterocyclyl, an aromatic or heteroaromatic moiety, -CF3, -CN, or the like.

The terms triflyl, tosyl, mesyl, and nonaflyl are art-recognized and refer to trifluoromethanesulfonyl, />-toluenesulfonyl, methanesulfonyl, and nonafluorobutanesulfonyl groups, respectively. The terms triflate, tosylate, mesylate, and nonaflate are art-recognized and refer to trifluoromethanesulfonate ester, p-toluenesulfonate ester, methanesulfonate ester, and nonafluorobutanesulfonate ester functional groups and molecules that contain said groups, respectively.

The abbreviations Me, Et, Ph, Tf, Nf, Ts, Ms represent methyl, ethyl, phenyl, trifluoromethanesulfonyl, nonafluorobutanesulfonyl, j9-toluenesulfonyl and methanesulfonyl, respectively. A more comprehensive list of the abbreviations utilized by organic chemists of ordinary skill in the art appears in the first issue of each volume of the Journal of Organic Chemistry; this list is typically presentd in a table entitled Standard List of Abbreviations. The abbreviations contained in said list, and all abbreviations utilized by organic chemists of ordinary skill in the art are hereby incorporated by reference.

As used herein, the term "nitro" means -NO2; the term "halogen" designates -F, -Cl, -Br or -I; the term "sulfhydryl" means -SH; the term "hydroxyl" means -OH; and the term "sulfonyl" means -SO2-.

The terms "amine" and "amino" are art-recognized and refer to both unsubstituted and substituted amines, e.g., a moiety that may be represented by the general formulas:

wherein R50, R51 and R52 each independently represent a hydrogen, an alkyl, an alkenyl, - (CH₂)_m-R61, or R50 and R51, taken together with the N atom to which they are attached complete a heterocycle having from 4 to 8 atoms in the ring structure; R61 represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and m is zero or an integer in the range of 1 to 8. In other embodiments, R50 and R51 (and optionally R52) each independently represent a hydrogen, an alkyl, an alkenyl, or -(CH₂)_m-R61. Thus, the term "alkylamine" includes an amine group, as defined above, having a substituted or unsubstituted alkyl attached thereto, i.e., at least one of R50 and R51 is an alkyl group.

The term "acylamino" is art-recognized and refers to a moiety that may be represented by the general formula:

wherein R50 is as defined above, and R54 represents a hydrogen, an alkyl, an alkenyl or - (CH₂)_m-R61, where m and R61 are as defined above.

The term "amido" is art recognized as an amino-substituted carbonyl and includes a moiety that may be represented by the general formula: wherein R50 and R51 are as defined above. Certain embodiments of the amide in the present invention will not include imides which may be unstable.

The term "alkylthio" refers to an alkyl group, as defined above, having a sulfur radical attached thereto. In certain embodiments, the "alkylthio" moiety is represented by one of -S-alkyl, -S-alkenyl, -S-alkynyl, and -S-(CH₂)_m-R61, wherein m and R61 are defined above. Representative alkylthio groups include methylthio, ethyl thio, and the like.

The term "carboxyl" is art recognized and includes such moieties as may be represented by the general formulas:

wherein X50 is a bond or represents an oxygen or a sulfur, and R55 and R56 represents a hydrogen, an alkyl, an alkenyl, -(CH₂)_m-R61or a pharmaceutically acceptable salt, R56 represents a hydrogen, an alkyl, an alkenyl or -(CH₂)_m-R61, where m and R61 are defined above. Where X50 is an oxygen and R55 or R56 is not hydrogen, the formula represents an "ester". Where X50 is an oxygen, and R55 is as defined above, the moiety is referred to herein as a carboxyl group, and particularly when R55 is a hydrogen, the formula represents a "carboxylic acid". Where X50 is an oxygen, and R56 is hydrogen, the formula represents a "formate". In general, where the oxygen atom of the above formula is replaced by sulfur, the formula represents a "thiolcarbonyl" group. Where X50 is a sulfur and R55 or R56 is not hydrogen, the formula represents a "thiolester." Where X50 is a sulfur and R55 is hydrogen, the formula represents a "thiolcarboxylic acid." Where X50 is a sulfur and R56 is hydrogen, the formula represents a "thiolformate." On the other hand, where X50 is a bond, and R55 is not hydrogen, the above formula represents a "ketone" group. Where X50 is a bond, and R55 is hydrogen, the above formula represents an "aldehyde" group.

The term "carbamoyl" refers to -0(C=O)NRR', where R and R¹ are independently H, aliphatic groups, aryl groups or heteroaryl groups. The term "oxo" refers to a carbonyl oxygen (=0).

The terms "oxime" and "oxime ether" are art-recognized and refer to moieties that may be represented by the general formula:

wherein R75 is hydrogen, alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or -(CH₂)_m-R61. The moiety is an "oxime" when R is H; and it is an "oxime ether" when R is alkyl, cycloalkyl, alkenyl, alkynyl, aryl, aralkyl, or -(CH₂)_m-R61.

The terms "alkoxyl" or "alkoxy" are art-recognized and refer to an alkyl group, as defined above, having an oxygen radical attached thereto. Representative alkoxyl groups include methoxy, ethoxy, propyloxy, tert-butoxy and the like. An "ether" is two hydrocarbons covalently linked by an oxygen. Accordingly, the substituent of an alkyl that renders that alkyl an ether is or resembles an alkoxyl, such as may be represented by one of -O-alkyl, -O-alkenyl, -O-alkynyl, -O~(CH₂)_m-R61, where m and R61 are described above.

The term "sulfonate" is art recognized and refers to a moiety that may be represented by the general formula:

in which R57 is an electron pair, hydrogen, alkyl, cycloalkyl, or aryl.

The term "sulfate" is art recognized and includes a moiety that may be represented by the general formula:

in which R57 is as defined above. The term "sulfonamido" is art recognized and includes a moiety that may be represented by the general formula:

in which R50 and R56 are as defined above. The term "sulfamoyl" is art-recognized and refers to a moiety that may be represented by the general formula:

in which R50 and R51 are as defined above.

The term "sulfonyl" is art-recognized and refers to a moiety that may be represented by the general formula:

in which R58 is one of the following: hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, heterocyclyl, aryl or heteroaryl.

The term "sulfoxido" is art-recognized and refers to a moiety that may be represented by the general formula:

in which R58 is defined above. The term "phosphoryl" is art-recognized and may in general be represented by the formula: wherein Q50 represents S or O, and R59 represents hydrogen, a lower alkyl or an aryl. When used to substitute, e.g., an alkyl, the phosphoryl group of the phosphorylalkyl may be represented by the general formulas:

wherein Q50 and R59, each independently, are defined above, and Q51 represents O, S or N. When Q50 is S, the phosphoryl moiety is a "phosphorothioate".

The term "phosphoramidite" is art-recognized and may be represented in the general formulas:

wherein Q51, R50, R51 and R59 are as defined above.

The term "phosphonamidite" is art-recognized and may be represented in the general formulas:

wherein Q51, R50, R51 and R59 are as defined above, and R60 represents a lower alkyl or an aryl. Analogous substitutions may be made to alkenyl and alkynyl groups to produce, for example, aminoalkenyls, aminoalkynyls, amidoalkenyls, amidoalkynyls, iminoalkenyls, iminoalkynyls, thioalkenyls, thioalkynyls, carbonyl-substituted alkenyls or alkynyls.

The definition of each expression, e.g. alkyl, m, n, and the like, when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.

The term "selenoalkyl" is art-recognized and refers to an alkyl group having a substituted seleno group attached thereto. Exemplary "selenoethers" which may be substituted on the alkyl are selected from one of -Se-alkyl, -Se-alkenyl, -Se-alkynyl, and - Se~(CH₂)_m-R61, m and R61 being defined above.

Analogous substitutions can be made to alkenyl and alkynyl groups to produce, for example, aminoalkenyls, aminoalkynyls, amidoalkenyls, amidoalkynyls, iminoalkenyls, iminoalkynyls, thioalkenyls, thioalkynyls, carbonyl-substituted alkenyls or alkynyls.

As used herein, the definition of each expression, e.g., alkyl, m, n, etc., when it occurs more than once in any structure, is intended to be independent of its definition elsewhere in the same structure.

It will be understood that "substitution" or "substituted with" includes the implicit proviso that such substitution is in accordance with permitted valence of the substituted atom and the substituent, and that the substitution results in a stable compound, e.g., which does not spontaneously undergo transformation such as by rearrangement, cyclization, elimination, etc.

As used herein, the term "substituted" is contemplated to include all permissible substituents of organic compounds. In a broad aspect, the permissible substituents include acyclic and cyclic, branched and unbranched, carbocyclic and heterocyclic, aromatic and nonaromatic substituents of organic compounds. Illustrative substituents include, for example, those described herein above. The permissible substituents can be one or more and the same or different for appropriate organic compounds. For purposes of this invention, the heteroatoms such as nitrogen may have hydrogen substituents and/or any permissible substituents of organic compounds described herein which satisfy the valences of the heteroatoms. This invention is not intended to be limited in any manner by the permissible substituents of organic compounds. The phrase "protecting group" as used herein means temporary substituents which protect a potentially reactive functional group from undesired chemical transformations. Examples of such protecting groups include esters of carboxylic acids, silyl ethers of alcohols, and acetals and ketals of aldehydes and ketones, respectively. The field of protecting group chemistry has been reviewed (Greene, T.W.; Wuts, P.G.M. Protective Groups in Organic Synthesis, 2^nd ed.; Wiley: New York, 1991).

Certain compounds of the present invention may exist in particular geometric or stereoisomeric forms. The present invention contemplates all such compounds, including cis- and /rα«s-isomers, R- and iS'-enantiomers, diastereomers, (D)-isomers, (L)-isomers, the racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the invention. Additional asymmetric carbon atoms may be present in a substituent such as an alkyl group. AU such isomers, as well as mixtures thereof, are intended to be included in this invention.

If, for instance, a particular enantiomer of a compound of the present invention is desired, it may be prepared by asymmetric synthesis, or by derivation with a chiral auxiliary, where the resulting diastereomeric mixture is separated and the auxiliary group cleaved to provide the pure desired enantiomers. Alternatively, where the molecule contains a basic functional group, such as amino, or an acidic functional group, such as carboxyl, diastereomeric salts are formed with an appropriate optically-active acid or base, followed by resolution of the diastereomers thus formed by fractional crystallization or chromatographic means well known in the art, and subsequent recovery of the pure enantiomers.

Contemplated equivalents of the compounds described above include compounds which otherwise correspond thereto, and which have the same general properties thereof (e.g., functioning as analgesics), wherein one or more simple variations of substituents are made which do not adversely affect the efficacy of the compound in binding to sigma receptors. In general, the compounds of the present invention may be prepared by the methods illustrated in the general reaction schemes as, for example, described below, or by modifications thereof, using readily available starting materials, reagents and conventional synthesis procedures. In these reactions, it is also possible to make use of variants which are in themselves known, but are not mentioned here. The term "alkali metal" refer to those elements listed in Group 1 of the periodic table. The following elements are alkali metals: Li, Na, K, Rb, Cs, and Fr.

For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 67th Ed., 1986-87, inside cover.

Compositions of the Invention

One aspect of the present invention relates to a lens composition comprising nanoparticles and a non-reversible hydrogel. In certain embodiments, the present invention relates to the aforementioned composition, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate. '

In certain embodiments, the present invention relates to the aforementioned composition, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule formed by treating a dendrimeric compound of formula Ia or formula Ib with a polymerization agent selected from the group consisting of ultraviolet light, visible light, compound II, compound in, compound IV, and compound V; wherein formula Ia is represented by:

A¹— X¹-B— X¹— A²

Ia wherein

A is alkyl, aryl, aralkyl, -Si(R )₃, or

A represents independently for each occurrence alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or aralkyl;

Y¹ represents independently for each occurrence R⁴, A⁴,

Z¹ represents independently for each occurrence -X¹-R⁴ , E, or

Y² represents independently for each occurrence R⁵, A⁴,

Z represents independently for each occurrence -X 1 -R r>5 , E, or

Y³ represents independently for each occurrence R⁶, A⁴,

Z represents independently for each occurrence -X 1 - rR> 6 , E, or

Y⁴ represents independently for each occurrence R⁷, A⁴,

Z⁴ represents independently for each occurrence -X¹ -R⁷, E, or

Y⁵ represents independently for each occurrence R⁸, A⁴,

Z⁵ represents independently for each occurrence -X¹-R⁸, E, or

Y⁶ represents independently for each occurrence R⁹, A⁴,

R¹ represents independently for each occurrence H, alkyl, or halogen; R² represents independently for each occurrence H, alkyl, -OH, -N(R^I0)₂, -SH, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R³ represents independently for each occurrence alkyl, aryl, or aralkyl; R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are H; R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl;

R¹¹ represents independently for each occurrence H, -OH, -N(R¹ °)₂, -SH, alkyl, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R¹² represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹³ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹⁴ represents independently for each occurrence H, alkyl, or -CO₂R¹⁰;

R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl,. imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is O, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5; X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-; X³ represents independently for each occurrence O, N(R¹⁰), or C(R¹⁵)(CO₂R¹⁰);

A represents independently for each occurrence

E represents independently for each occurrence

provided that R⁴OnIy occurs once, R⁵ only occurs once, R⁶ only occurs once, R⁷ only occurs once, R⁸ only occurs once, and R⁹ only occurs once; said formula Ib is represented by:

or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁵ represents independently for each occurrence O or -N(R²²)-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

C(O)(C(R^I9)₂)_hSH, -CO₂(C(R¹⁹)₂)hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH,

R¹⁸ represents independently for each occurrence H or alkyl; R¹⁹ represents independently for each occurrence H, halogen, or alkyl; R²⁰ represents independently for each occurrence H or alkyl; R²¹ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

C(O)(C(R¹⁹)₂)_hSH, -CO₂(C(R¹⁹)₂)_hSH, -C(O)N(R¹⁸XC(R¹⁹)₂)_hSH, or

R²² represents independently for each occurrence H, alkyl, aryl, or aralkyl; n¹ and h each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; p⁵ represents independently for each occurrence 1, 2, 3, 4, or 5; v represents independently for each occurrence 2, 3, or 4; and w is an integer in the range of about 5 to about 700, inclusive; said compound II is represented by:

wherein

R^1-II represents independently for each occurrence H or

R^2-II represents independently for each occurrence H or alkyl;

R^3-II represents independently for each occurrence H, halogen, or alkyl;

R^4-II represents independently for each occurrence alkyl, aryl, or aralkyl; and

R^5"11 represents independently for each occurrence H or and z represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; said compound III is represented by:

wherein R^1-111 is -(C(R²-^IU)₂)_XC(O)H, -C(O)(C(R²-^IU)₂)_yC(O)H, -(C(R²-^ΠI)₂)_XC(O)R³-^ΠI, or -

C(O)(C(R²-^πI)₂)_yC(O)R³-^πi;

R^2-111 represents independently for each occurrence H, alkyl, or halogen; R ,3^>-m^m is fluσroalkyl, chloroalkyl, -CH₂NO₂, or

B is alkyl diradical, heteroalkyl diradical,

x represents independently for each occurrence 0, 1, 2, 3, 4, 5, 6, 7, or 8;

y represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8;

v represents independently for each occurrence 2, 3, or 4; and

w is an integer in the range of about 5 to about 700, inclusive;

said compound IV is represented by:

wherein

A 2 is alkyl, aryl, aralkyl,r -Si(R³ )₃,

A represents independently for each occurrence alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or aralkyl; Z¹ represents independently for each occurrence -X¹ -R⁴, E, or

Y² represents independently for each occurrence R⁵,

Z represents independently for each occurrence -X ¹-R⁵ , E, or

Y³ represents independently for each occurrence R ,

Z³ represents independently for each occurrence -X¹ -R⁶ , E, or

Z⁴ represents independently for each occurrence -X¹ -R⁷, E, or

6

Y represents independently for each occurrence R ,

Z⁵ represents independently for each occurrence -X¹-R⁸, E, or

Y represents independently for each occurrence R ,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R represents independently for each occurrence H, alkyl, -OH, -N(R )₂, -SH, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R³ represents independently for each occurrence alkyl, aryl, or aralkyl;

R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are H;

R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹ °)₂, -SH, alkyl, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R¹² represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹³ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹⁴ represents independently for each occurrence H, alkyl, or -CO₂R¹⁰; R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R^l0)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹ °)₂; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is 0, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-;

X³ represents independently for each occurrence O, N(R¹⁰), or C(R¹⁵)(CO₂R¹⁰); and

E represents independently for each occurrence H, and said compound V is represented by:

or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁶ represents independently for each occurrence O or -N(R³⁰)-;

R²³ represents independently for each occurrence R²⁴ represents independently for each occurrence H or alkyl;

R²⁵ represents independently for each occurrence H, halogen, or alkyl;

R²⁶ represents independently for each occurrence H or alkyl;

R²⁷ represents independently for each occurrence H, alkyl, or halogen;

R²⁸ represents independently for each occurrence H, alkyl, -OH, -N(R³⁰)₂, -SH, or hydroxyalkyl;

R²⁹ represents independently for each occurrence H, -OH, -N(R³⁰)₂, -SH, alkyl, or hydroxyalkyl;

R³⁰ and R³¹ represent independently for each occurrence H, alkyl, aryl, or aralkyl; Z⁶ represents independently for each occurrence E¹ or

R represents independently for each occurrence

Z⁷ represents independently for each occurrence E¹ or

R >33 represents independently for each

R³⁴ represents independently for each occurrence H, alkyl, or -CO₂R 30,

E represents independently for each occurrence H, -[C(R ²⁴)₂]jC(O)H, or

p represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p⁷ represents independently for each occurrence 0, 1, 2, 3, or 4; p represents independently for each occurrence 1, 2, or 3; p⁹ represents independently for each occurrence 0, 1, 2, or 3; n² and j each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; m¹ represents independently for each occurrence 1 or 2; v represents independently for each occurrence 2, 3, or 4; and w is an integer in the range of about 5 to about 700, inclusive.

In certain instances, the present invention relates to the aforementioned composition, wherein said dendrimeric compound is compound of formula Ia, and said polymerization agent is ultraviolet light, visible light, compound II, or compound III.

In certain instances, the present invention relates to the aforementioned composition,

wherein A is , and m is 1 or 2. In certain instances, the present invention relates to the aforementioned composition,

wherein A is

, or -Si(R³)₃..; wherein, m is 1 or 2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z¹ represents independently for each occurrence -X¹ -R⁴ or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z² represents independently for each occurrence -X¹ -R⁵ or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z³ represents independently for each occurrence -X¹ -R⁶ or

In certain instances, the present invention relates to the aforementioned composition, wherein Z⁴ represents independently for each occurrence -X¹ -R⁷ or

2. In certain instances, the present invention relates to the aforementioned composition, wherein Z⁵ represents independently for each occurrence -X'-R⁸ or

In certain instances, the present invention relates to the aforementioned composition, wherein X¹ is O.

In certain instances, the present invention relates to the aforementioned composition, wherein X¹ and X² are O.

In certain instances, the present invention relates to the aforementioned composition, wherein n is 1. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, 3, or 4.

In certain instances, the present invention relates to the aforementioned composition, wherein p² is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein R¹ is H.

wherein B is

wherein R¹ is H, B m

wherein R¹ is H, B is m

and said polymerization agent is ultraviolet light or visible light.

wherein R¹ is H, B is A² is m

and said polymerization agent is compound III. In certain instances, the present invention relates to the aforementioned composition,

m wherein R¹ is H, B i s

groups are H, and about 1/2 of the Y groups are ^x ' P

, about 1/2 of the Y⁴

groups are H, about 1/2 of the Y⁴ groups are and said polymerization agent is ultraviolet light or visible light. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is H, B is , m

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 1, 2, 3, or 4.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 4. In certain instances, the present invention relates to the aforementioned composition, wherein m is 1.

wherein B is

wherein R¹ is H, B is , m is 1

wherein R¹ is H, B , m is 1

or visible light.

wherein R¹ is H, B is , m is 1

and said polymerization agent is compound III.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 4.

In certain instances, the present invention relates to the aforementioned composition, wherein m is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein R² is (C_rC₃)alkyl.

wherein B is

wherein R¹ is H, B and v¹ is 2.

wherein R¹ is H, B is o P^I' v¹ is 2, A² , m is 1 or 2, Y¹ is /D¹ and Z¹ is

polymerization agent is ultraviolet light or visible light.

wherein R¹ is H₃ B is , v¹ is 2, A²

wherein R¹ is H, B is

wherein R¹ is H, B is v¹ is 2, A²

polymerization agent is ultraviolet light or visible light.

wherein R¹ is H, B is v¹ is 2, A²

IS Z¹ is

polymerization agent is ultraviolet light or visible light.

wherein R¹ is H, B is P^I , v' is 2, A² is

m

In certain instances, the present invention relates to the aforementioned composition, wherin w¹ is an integer in the range of about 50 to about 250.

In certain instances, the present invention relates to the aforementioned composition, wherein w¹ is an integer in the range of about 60 to about 90. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (C₁-C₅)alkyl.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, R³ is (Ci-C₅)alkyl, and w¹ is an integer in the range of about 60 to about 90. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is H, B is A² is R³ is alkyl, v² i IS

wherein R¹ is H, B is , R³ is alkyl, v² is

is

_R ³ _{is alkylj V}2 _is

and said polymerization agent is ultraviolet light or visible light. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is H, B is A² is , R³ is alkyl, Ψ is

wherein R¹ is H, B is A² is , R³ is alkyl, v² i IS

P , and said polymerization agent is ultraviolet light or visible light.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (C₁-C₅)alkyl. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is^l(Ci-C₅)alkyl, and w² is an integer in the range of about 60 to about 90.

wherein R¹ is H, B is m

m

wherein R¹ is H, B is , m

wherein R¹ is H, B is m

In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is compound II. In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is compound III.

In certain instances, the present invention relates to the aforementioned composition, wherein said polymerization agent is compound III, R^1"111 is -C(O)H, and R^2"111 is H.

In certain instances, the present invention relates to the aforementioned composition, wherein said polymerization agent is compound III, R^1"111 is -C(O)H, R^2"111 is H, and B^1"111 is

In certain instances, the present invention relates to the aforementioned composition, wherein said polymerization agent is compound III, R^2"m is -C(O)H, R^2"111 is H, B^1"111 is

and w is an integer in the range of about 60-90.

In certain instances, the present invention relates to the aforementioned composition, wherein said compound of formula Ia is

is an integer in the range of about 70 to about 80, and said polymerization agent is UV light.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said dendrimeric compound is a compound of formula Ib. In certain embodiments, the present invention relates to the aforementioned composition, wherein v is 2.

In certain embodiments, the present invention relates to the aforementioned composition, wherein X⁵ is -N(H)-.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R¹⁸ is H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R¹⁹ is H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R²⁰ is H. In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 20-500.

In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 40-250.

In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 60-90.

In certain embodiments, the present invention relates to the composition, said compound of formula Ib is

In certain embodiments, the present invention relates to the aforementioned composition, said polymerization agent is compound V.

Ill In certain embodiments, the present invention relates to the aforementioned composition, wherein v is 2.

In certain embodiments, the present invention relates to the aforementioned composition, wherein X⁶ is -N(H)-. In certain embodiments, the present invention relates to the aforementioned composition, wherein R²⁴ is H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R²⁵ is H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R²⁶ is H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 20-500.

In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 40-250. In certain embodiments, the present invention relates to the aforementioned composition, wherein w is an integer in the range of about 60-90.

In certain embodiments, the present invention relates to the aforementioned composition, wherein R²³ represents independently for each occurrence

In certain embodiments, the present invention relates to the aforementioned composition, said compound V is o

In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is ultraviolet light or visible light.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is ultraviolet light.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is light with a λ of 400-600 nm.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is light with a λ of 450-550 nm. In certain embodiments, the present invention relates to the aforementioned composition, wherein said polymerization agent is light with a λ of 488-514 nm.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VI with a polymerization agent represented by formula VII, wherein formula VI is represented by:

VI or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein R¹ represents independently for each occurrence H, -(C(R³)₂)_mSH, -

C(O)(C(R³)₂)_mSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

R² represents independently for each occurrence H or alkyl; R³ represents independently for each occurrence H, halogen, or alkyl;

R⁴ represents independently for each occurrence alkyl, aryl, or aralkyl; R⁵ represents independently for each occurrence -(C(R³)₂)_mSH, -C(O)(C(R³)₂)_mSH, -

CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH, n and m each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; p is 1, 2, 3, 4, or 5; and formula VII is represented by:

wherein

R¹-™ represents independently for each occurrence -(C(R^2-vιι)₂)_xC(O)H, -C(O)(C(R²-

^VII)₂)_yC(O)H, -(C(R²-^vπ)₂)_xC(O)R³-^VII, -C(O)(C(R²-^vπ)₂)_yC(O)R³-^vπ,

R^2-vιι represents independently for each occurrence H, alkyl, or halogen; R ,3^J-^"V^VI^UI is is fluoroalkyl, chloroalkyl, -CH₂NO

B is alkyl diradical, heteroalkyl diradical, or v .,2-VII represents independently for each occurrence 2, 3, or 4; and w^2"vπ is an integer in the range of about 5 to 700, inclusive.

In certain instances, the present invention relates to the aforementioned composition, w^2"vπ is an integer in the range of about 50 to about 250.

In certain instances, the present invention relates to the aforementioned composition, w^2"vπ is an integer in the range of about 60 to about 90.

In certain instances, the present invention relates to the aforementioned composition, whe erreeiin said polymerization agent is a compound of formula VII, R^2"VI1 is -C(O)H, and R^2" ^vπ is H.

In certain instances, the present invention relates to the aforementioned composition, wherein said polymerization agent is a compound of formula VII, R^2~vπ is -C(O)H, R^2-vιι is

H, B is and v ,,2^z--V^vI^lI^l i . s 2. In certain instances, the present invention relates to the aforementioned composition, wherein said polymerization agent is a compound of formula VII, R^2'vπ is -C(O)H, R^2~vπ is

H, B is ^-VH _{is an integer in the range of} about 60-90.

In certain instances, the present invention relates to the aforementioned composition, wherein n is 3, 4, or 5.

In certain instances, the present invention relates to the aforementioned composition, wherein n is 4. In certain instances, the present invention relates to the aforementioned composition, wherein R² is H.

In certain instances, the present invention relates to the aforementioned composition, wherein R³ is H. In certain instances, the present invention relates to the aforementioned composition, wherein R⁴ is alkyl.

In certain instances, the present invention relates to the aforementioned composition, wherein R⁴ is methyl or ethyl.

In certain instances, the present invention relates to the aforementioned composition, wherein n is 4, R² and R³ is H, and R⁴ is alkyl.

wherein R¹ is and p is 1. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is

wherein R¹ and p is l.

wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is and p is 1. In certain instances, the present invention relates to the aforementioned composition,

wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is and p is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and a Bronstead acid.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and HA, wherein A is halogen or -O₂CR⁶, and R⁶ is alkyl, fluoroalkyl, aryl, or aralkyl. In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and an acid selected from group consisting of HCl and HBr.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and HO₂CR⁶, wherein R⁶ is fluoroalkyl.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and CF₃CO₂H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are present in about 1 to about 40 weight percent.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are present in about 5 to about 25 weight percent. In certain embodiments, the present invention relates to the aforementioned composition, wherein the diameter of said microparticles is less than about 50 nm.

In certain embodiments, the present invention relates to the aforementioned composition, wherein the diameter of said microparticles is less than about 20 nm.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens. In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens is transparent.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens swells less than about 100% in aqueous solution. In certain embodiments, the present invention relates to the aforementioned composition, further comprising a material that absorbs ultraviolet light.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^"3.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^"5.

In certain embodiments, the present invention relates to the aforementioned composition, wherein less than about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned composition, wherein less than about 15% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned composition, wherein less than about 5% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond. In certain embodiments, the present invention relates to the aforementioned composition, wherein less than about 1% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

Another aspect of the present invention relates to a lens composition comprising nanoparticles and a reversible hydrogel, wherein said hydrogel comprises a dendrimeric macromolecule.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene- ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VIII or formula IX with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formula VIII is represented by: )

A¹— X¹-B— X¹— A²

VIII wherein

A² is alkyl, aryl, aralkyl, -Si(R^J)₃, or

Y¹ represents independently for each occurrence R⁴,

Z¹ represents independently for each occurrence -X¹ -R⁴ , E, or

Y² represents independently for each occurrence R⁵,

Z² represents independently for each occurrence -X¹ -R⁵, E, or

Y represents independently for each occurrence R ,

Z³ represents independently for each occurrence -X ¹-R⁶ , E, or

Y⁴ represents independently for each occurrence R⁷,

z⁴- represents independently for each occurrence -X¹ -R⁷, E, or

Y⁵ represents independently for each occurrence R⁸,

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y⁶ represents independently for each occurrence R⁹,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R represents independently for each occurrence H, alkyl, -OH, -N(R ¹⁰)₂, -SH, hydroxyalkyl, or -[C(R¹)₂] _dR¹⁶;

R³ represents independently for each occurrence alkyl, aryl, or aralkyl;

R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are H;

R , 10 represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹ °)₂, -SH, alkyl, hydroxyalkyl, or -[CtR^R¹⁶;

R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence O₅ 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4;

) w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is l, 2, or 3; y is 0, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-; X³ represents independently for each occurrence O, N(R¹⁰), or C(R^1S)(CO₂R¹⁰);

provided that R⁴ only occurs once, R⁵ only occurs once, R⁶ only occurs once, R⁷ only occurs once, R⁸ only occurs once, and R⁹ only occurs once; said formula IX is represented by:

IX or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X^s represents independently for each occurrence O or -N(R²²)-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

C(O)(C(R¹⁹)₂)_hSH, -CO₂(C(R¹⁹)₂)_hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH,

R¹⁸ represents independently for each occurrence H or alkyl;

R¹⁹ represents independently for each occurrence H, halogen, or alkyl;

R²⁰ represents independently for each occurrence H or alkyl; R²¹ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

C(O)(C(R¹⁹)₂)_hSH, -CO₂(C(R¹⁹)₂)_hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH, or

R ,22 represents independently for each occurrence H, alkyl, aryl, or aralkyl; n¹ and h each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; p⁵ represents independently for each occurrence 1, 2, 3, 4, or 5; v represents independently for each occurrence 2, 3, or 4; and w is an integer in the range of about 5 to about 700, inclusive.

In certain instances, the present invention relates to the aforementioned composition, wherein a compound of formula VIII contains at least two thiol groups.

In certain instances, the present invention relates to the aforementioned composition, wherein a compound of formula VIII contains at least five thiol groups. In certain instances, the present invention relates to the aforementioned composition, wherein a compound of formula IX contains at least two thiol groups.

In certain instances, the present invention relates to the aforementioned composition, wherein a compound of formula IX contains at least five thiol groups.

wherein A¹ , and m is 1 or 2.

wherein A² is

, or -Si(R³)₃; wherein, m is 1 or 2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z¹ represents independently for each occurrence -X*-R⁴ or

2. In certain instances, the present invention relates to the aforementioned composition, wherein Z² represents independently for each occurrence -X ¹-R⁵ or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z represents independently for each occurrence -X 1 - nR7 or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z⁵ represents independently for each occurrence -X¹ -R⁸ or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein X¹ is O. In certain instances, the present invention relates to the aforementioned composition, wherein X¹ and X² are O.

In certain instances, the present invention relates to the aforementioned composition, wherein n is i.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, 3, or 4. In certain instances, the present invention relates to the aforementioned composition, wherein p² is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein R¹ is H. In certain instances, the present invention relates to the aforementioned composition,

wherein B i

wherein R¹ is H, B is m

is l or 2, Y¹ is In certain instances, the present invention relates to the aforementioned composition,

wherein R¹

wherein R¹ is H, B is , m

wherein R¹ is H, B is m

about 1/2 of the Y⁴

groups are H, and about 1/2 of the Y groups are

wherein R¹ is H, B is m

In certain instances, the present invention relates to the aforementioned composition, wherein m is 1. In certain instances, the present invention relates to the aforementioned composition,

wherein B is

wherein R¹ is H, B is , m is 1

wherein R¹ is H, B is

In certain instances, the present invention relates to the aforementioned composition, wherein R² is (d-C₃)alkyl.

wherein B is

wherein R¹ is H, B is and v¹ is 2. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is H, B is v¹ is 2, A²

, m is 1 or 2, Y¹ is P¹ , and Z¹ is

wherein R¹ is H, B is v¹ is 2, K-

wherein R¹ is H, B is v¹ is 2, A²

In certain instances, the present invention relates to the aforementioned composition, wherein w¹ is an integer in the range of about 60 to about 90.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (Ci-C₅)alkyl. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, R³ is (C₁-Cs)alkyl, and w¹ is an integer in the range of about 60 to about 90.

wherein R¹ is H, B is A² is , R³ is alkyl, v² is

wherein R¹ is H, B is , R³ is alkyl,v² is

wherein R¹ is H, B is A² is , R³ is alkyl, v² is

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2. In certain instances, the present invention relates to the aforementioned composition, wherein m is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is O, and R³ is (C₁-C₅)alkyl. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (Ci-Cs)alkyl, and w² is an integer in the range of about 60 to about 90.

wherein R¹ is H, B is m

wherein R¹ is H, B is , m IS 1, or 2, Y¹ IS , Y² is

wherein R¹ is H, B , m

In certain instances, the present invention relates to the aforementioned composition, wherein said dendrimeric molecule is

, n is an integer in the range of about 70 to about 80, and said polymerization agent is O₂.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said dendrimeric compound is a compound of formula IX. In certain embodiments, the present invention relates to the aforementioned composition, wherein v is 2.

In certain embodiments, the present invention relates to the aforementioned composition, wherein X^s is -N(H)-.

In certain embodiments, the present invention relates to the aforementioned composition, said compound of formula IX is:

In certain embodiments, the present invention relates to the aforementioned composition, wherein said oxidizing agent is O₂.

In certain embodiments, the present invention relates to the aforementioned composition, wherein about 1% to about 70% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned composition, wherein about 5% to about 50% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond. In certain embodiments, the present invention relates to the aforementioned composition, wherein about 5% to about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula X with an oxidizing agent sufficient to polymerize said compound of formula X, wherein formula X is represented by:

X or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

R¹ represents independently for each occurrence H, -(C(R³)₂)_mSH, -

C(O)(C(R³)₂)_mSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

R² represents independently for each occurrence H or alkyl;

R³ represents independently for each occurrence H, halogen, or alkyl;

R⁴ represents independently for each occurrence alkyl, aryl, or aralkyl; R⁵ represents independently for each occurrence -(C(R³)₂)_mSH, -C(O)(C(R³)₂)_mSH_; -

CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH, n and m each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; and p is 1, 2, 3, 4, or 5. In certain instances, the present invention relates to the aforementioned composition, wherein said compound of formula X has at least two thiol groups.

In certain instances, the present invention relates to the aforementioned composition, wherein said compound of formula X has at least five thiol groups.

In certain instances, the present invention relates to the aforementioned composition, wherein n is 4.

In certain instances, the present invention relates to the aforementioned composition, wherein R² is H. In certain instances, the present invention relates to the aforementioned composition, wherein R³ is H.

In certain instances, the present invention relates to the aforementioned composition, wherein R⁴ is alkyl.

wherein R¹ is In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is and p is 1.

wherein R¹ is

wherein R¹ is and p is l.

wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is and p is 1.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and a Bronstead acid.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HA, wherein A is halogen or -O₂CR⁶, and R⁶ is alkyl, fluoroalkyl, aryl, or aralkyl.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and an acid selected from group consisting of HCl and HBr. In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HO₂CR⁶, wherein R⁶ is fluoroalkyl.

In certain instances, the present invention relates to the aforementioned composition, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and CF₃CO₂H.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are covalently bonded to said dendrimeric macromolecule.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are present in about 1 to about 40 weight percent.

Another aspect of the present invention relates to a lens composition comprising nanoparticles and a reversible hydrogel, wherein said nanoparticles have a core made of a metal, metal sulfide, zeolite, ceramic, diamond, titanium dioxide, zinc oxide, aluminium oxide, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, carbon, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel comprises a dendrimeric macromolecule.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VIQ or formula IX with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formula VIII is represented by:

A¹— X¹-B— X¹— A² VIII wherein

or

Y¹ represents independently for each occurrence R⁴,

Z¹ represents independently for each occurrence -X¹ -R⁴ E, or

Y represents independently for each occurrence R⁵,

Z² represents independently for each occurrence -X¹ -R⁵, E, or

Y³ represents independently for each occurrence R⁶,

Z³ represents independently for each occurrence -X ¹-R⁶ , E, or

Y⁴ represents independently for each occurrence R⁷,

Z⁴ represents independently for each occurrence -X¹ -R⁷, E, or

Y represents independently for each occurrence R⁸,

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y represents independently for each occurrence R⁹,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R² represents independently for each occurrence H, alkyl, -OH, -N(R^I0)₂, -SH, hydroxyalkyl, or -[C(R¹^J_dR¹⁶;

R³ represents independently for each occurrence alkyl, aryl, or aralkyl; R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are H; R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹⁰)₂, -SH, alkyl, hydroxyalkyl, or -[qR¹)^¹⁶;

R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is 0, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-; X³ represents independently for each occurrence O, N(R¹⁰), or C(R¹⁵)(CO₂R¹⁰);

IX or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁵ represents independently for each occurrence O or -N(R²²)-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH,

-CO₂(C(R , 1ⁱ9^yN)₂)_hSH, -C(O)N(R , 1^l8^sx)(C(R ) 1ⁱ9^y)s₂)_hSH,

R¹⁸ represents independently for each occurrence H or alkyl;

R¹⁹ represents independently for each occurrence H, halogen, or alkyl;

R²⁰ represents independently for each occurrence H or alkyl;

R²¹ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

C(O)(C(R^I9)₂)_hSH, -CO₂(C(R¹⁹)₂)_hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH, or

R²² represents independently for each occurrence H, alkyl, aryl, or aralkyl; n¹ and h each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; p⁵ represents independently for each occurrence 1, 2, 3, 4, or 5; v represents independently for each occurrence 2, 3, or 4; and w is an integer in the range of about 5 to about 700, inclusive.

wherein A¹ , and m is 1 or 2.

wherein A² IS

, or -Si(R³)₃; wherein, m is 1 or 2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z¹ represents independently for each occurrence -X'-R⁴ or

2. In certain instances, the present invention relates to the aforementioned composition, wherein Z² represents independently for each occurrence -X¹ -R⁵ or

2.

In certain instances, the present invention relates to the aforementioned composition, wherein Z⁴ represents independently for each occurrence -X¹-R⁷ or

In certain instances, the present invention relates to the aforementioned composition, , wherein n is 1.

wherein B is

wherein R¹ is H, B is m

wherein R¹ is H, B is A² is , m

wherein R¹ is H, B is m

wherein R¹ is H, B is

groups are H, and about 1/2 of the Y⁴ groups are

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2. 2006/023723

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 4.

wherein B i is.

wherein R¹ is H, B is

wherein R¹ is H, B is , m is 1

wherein R¹ is H, B is A² is m is 1

or 2, Y¹ is Z¹ is Y² is

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2. ^" '

In certain instances, the present invention relates to the aforementioned composition, wherein R² is (Ci-C₃)alkyl.

wherein B is

wherein R¹ is H, B is , and v¹ is 2. In certain instances, the present invention relates to the aforementioned composition,

wherein R¹ is H, B is v¹ is 2, A²

IS m is 1 or 2, Y¹ is Z¹ is

wherein R¹ is H, B is A²

wherein R¹ is H, B is v¹ is 2, A²

wherein R¹ is H, B is v^! is 2, A²

In certain instances, the present invention relates to the aforementioned composition, wherin w¹ is an integer in the range of about 50 to about 250. i In certain instances, the present invention relates to the aforementioned composition, wherein w¹ is an integer in the range of about 60 to about 90.

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (Ci-Cs)alkyl. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, R³ is (Ci-C₅)alkyl, and w¹ is an integer in the range of about 60 to about 90.

wherein R¹ is H, B w² , R³ is alkyl, v² is

wherein R¹ is H, B is v¹ is 2, A²

wherein R¹ is H, B is , R³ is alkyl, v² is

wherein R¹ is H, B is R³ is alkyl, v² i is

In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is O, and R³ is (Ci-C₅)alkyl. In certain instances, the present invention relates to the aforementioned composition, wherein p¹ is 2, p² is 0, and R³ is (Ci-C₅)alkyl, and w² is an integer in the range of about 60 to about 90.

wherein R¹ is H, B is m

wherein R¹ is H, B is , m

wherein R¹ is H, B is m

In certain instances, the present invention relates to the aforementioned composition, wherein said compound of formula VIII is

, ii is an integer in the range of about 70 to about 80, and said polymerization agent

In certain embodiments, the present invention relates to the aforementioned composition, wherein R is H.

X or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

R¹ represents independently for each occurrence H, -(C(R³)₂)_mSH,

C(O)(C(R³)₂)_fflSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

R² represents independently for each occurrence H or alkyl;

R³ represents independently for each occurrence H, halogen, or alkyl;

wherein R¹ is and p is 1.

wherein R¹ is

wherein R¹ and p is 1.

wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is and p is 1.

wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is 1.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are present in about 5 to about 25 weight percent.

In certain embodiments, the present invention relates to the aforementioned composition, wherein the diameter of said microparticles is less than about 50 nm.

In certain embodiments, the present invention relates to the aforementioned composition, wherein the diameter of said microparticles is less than about 20 nm. In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens is transparent. In certain embodiments, the present invention relates to the aforementioned composition, wherein said lens swells less than about 100% in an aqueous solution.

In certain embodiments, the present invention relates to the aforementioned composition, further comprising a material that absorbs ultraviolet light.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^"3. In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^"5.

Another aspect of the present invention relates to a lens composition comprising nanoparticles and a hydrogel, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles remain dispersed when placed in an aqueous solution having a pH of about 7.0.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said hydrogel comprises a dendrimeric macromolecule. In certain embodiments, the present invention relates to the aforementioned composition, wherein said hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said hydrogel comprises a dendrimeric macromolecule formed by treating a dendrimeric compound of formula Ia or formula Ib with a polymerization agent selected from the group consisting of ultraviolet light, visible light, compound π, compound III, compound IV, and compound V; wherein formulae Ia, Ib, II, III, IV, and V are as defined above.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VQI, IX, or X with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formulae VIII, IX, and X are as defined above. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles. In certain embodiments, the present invention relates to the aforementioned composition, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^'3. In certain embodiments, the present invention relates to the aforementioned composition, wherein said composition has a sterility assurance level of at least about 10^"5.

Kits of the Invention

One aspect of the present invention relates to a kit for the preparation of a lens comprising: a polymerizable dendrimeric compound; nanoparticles; and a system for delivering said mixture to a lens bag of a patient.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said system is a syringe.

In certain embodiments, the present invention relates to the aforementioned kit, further comprising a capulorrhexis plug

In certain embodiments, the present invention relates to the aforementioned kit, further comprising a desiccant.

In certain embodiments, the present invention relates to the aforementioned kit, further comprising an inert atmosphere to prevent reaction of said dendrimeric compound or said nanoparticles with atmospheric molecules.

In certain embodiments, the present invention relates to the aforementioned kit, further comprising the polymerization agent.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said polymerization agent is compound II, compound III, compound IV, compound V, or compound VII; wherein compound II, compound III, compound IV, compound V, and compound VII are as defined above.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said polymerization agent is compound in or compound IV, and compound III and compound IV are as defined above. In certain embodiments, the present invention relates to the aforementioned kit, wherein said dendrimeric compound is represented by formula Ia, formula Ib, or formula VI; wherein formula Ia, formula Ib, and formula VI are as defined above.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said dendrimeric compound is represented by formula Ia or formula Ib, wherein formula Ia and formula Ib are as defined above.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said dendrimeric compound is represented by formula VIII, formula IX, or formula X; wherein formula VIII, formula IX, and formula X are as defined above. In certain embodiments, the present invention relates to the aforementioned kit, wherein said dendrimeric compound and nanoparticles are combined to form a mixture.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said kit has a sterility assurance level of at least about 10^"3.

In certain embodiments, the present invention relates to the aforementioned kit, wherein said kit has a sterility assurance level of at least about 10^'5.

Methods of the Invention

One aspect of the present invention relates to a method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a nonreversible hydrogel. In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture further comprises water.

In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene- styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2- hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate. In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerizable dendrimeric compound is represented by formula Ia or formula Ib₅ wherein formula Ia and formula Ib are as described above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerization agent is ultraviolet light, visible light, compound II, compound III, compound IV, or compound V; wherein compound II, compound III, compound IV, and compound V are as defined above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerizable dendrimeric compound is a compound of formula VI and said polymerization agent is a compound of formula VII, wherein formula VI and formula VII are as defined above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are present in about 1 to about 40 weight percent in said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are present in about 5 to about 25 weight percent in said hydrogel. In certain embodiments, the present invention relates to the aforementioned method, wherein the diameter of said microparticles is less than about 50 nm.

In certain embodiments, the present invention relates to the aforementioned method, wherein the diameter of said microparticles is less than about 20 nm.

In certain embodiments, the present invention relates to the aforementioned method, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

In certain embodiments, the present invention relates to the aforementioned method, wherein said lens is transparent.

In certain embodiments, the present invention relates to the aforementioned method, wherein said lens swells less than about 100% in aqueous solution.

In certain embodiments, the present invention relates to the aforementioned method, wherein said mixture further comprises a material that absorbs ultraviolet light.

In certain embodiments, the present invention relates to the aforementioned method, wherein said lens forms in vivo. In certain embodiments, the present invention relates to the aforementioned method, further comprising the steps of sterilizing said nanoparticles, and admixing said microparticles with the polymerizable dendrimeric compound to form said first mixture.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, further comprising the steps of sterilizing said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration. In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, further comprising the step of administering said first mixture to a lens bag of a patient.

In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5. In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH of about 7.4.

In certain embodiments, the present invention relates to the aforementioned method, wherein the step of administering the first mixture is performed using a syringe.

In certain embodiments, the present invention relates to the aforementioned method, further comprising the step of administering said second mixture to a lens bag of a patient. In certain embodiments, the present invention relates to the aforementioned method, wherein the step of administering the second mixture is performed using a syringe.

In certain embodiments, the present invention relates to the aforementioned method, wherein said second mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5. In certain embodiments, the present invention relates to the aforementioned method, wherein said second mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

In certain embodiments, the present invention relates to the aforementioned method, wherein said second mixture is an aqueous buffer solution that has a pH of about 7.4. In certain embodiments, the present invention relates to the aforementioned method, wherein said patient is a primate, equine, feline, or canine.

In certain embodiments, the present invention relates to the aforementioned method, wherein said patient is a human.

In certain embodiments, the present invention relates to the aforementioned method, wherein less than about 30% of the thiol groups present in said hydrogel form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned method, wherein less than about 15% of the thiol groups present in said hydrogel form a disulfide bond. In certain embodiments, the present invention relates to the aforementioned method, wherein less than about 5% of the thiol groups present in said hydrogel form a disulfide bond.

In certain embodiments, the present invention relates to the aforementioned method, wherein less than about 1% of the thiol groups present in said hydrogel form a disulfide bond.

Another aspect of the present invention relates to a method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a reversible hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said mixture further comprises water.

In certain embodiments, the present invention relates to the aforementioned method, wherein said mixture further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerizable dendrimeric compound is represented by formula VIII, formula IX, or formula X; wherein formula VIII, formula IX, and formula X are as defined above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerizable dendrimeric compound is represented by formula VIII, wherein formula VIII is as defined above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said polymerization agent is O₂. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

In certain embodiments, the present invention relates to the aforementioned method wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

In certain embodiments, the present invention relates to the aforementioned method, said mixture further comprises a material that absorbs ultraviolet light.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said nanoparticles. In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"s for said nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, further comprising the steps of sterilizing said hydrogel. In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about lO^'3 for said hydrogel.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said hydrogel. In certain embodiments, the present invention relates to the aforementioned method, further comprising the step of administering said first mixture to a lens bag of a patient.

In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5.

In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5. In certain embodiments, the present invention relates to the aforementioned method, wherein said first mixture is an aqueous buffer solution that has a pH of about 7.4.

Another aspect of the present invention relates to a method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a hydrogel, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

In certain embodiments, the present invention relates to the aforementioned method, wherein said mixture further comprises water. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles remain dispersed when placed in an aqueous solution having a pH of about 7.0.

In certain embodiments, the present invention relates to the aforementioned method, wherein said hydrogel comprises a dendrimeric macromolecule.

In certain embodiments, the present invention relates to the aforementioned method, wherein said dendrimeric compound is a compound of formula Ia or formula Ib, and said polymerization agent selected from the group consisting of ultraviolet light, visible light, compound II, compound III, compound IV, and compound V; wherein formulae Ia, Ib, π, III, IV, and V are as defined above.

In certain embodiments, the present invention relates to the aforementioned method, wherein said dendrimeric compound is a compound of formulae VIII, IX, or X, and said polymerization agent is an oxidizing agent, wherein formulae formulae VIII, IX, and X are as defined above. In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

In certain embodiments, the present invention relates to the aforementioned method, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an' organic compound.

In certain embodiments, the present invention relates to the aforementioned method, further comprising the step of sterilizing said nanoparticles and said polymerizable compound.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration. In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3.

In certain embodiments, the present invention relates to the aforementioned method, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5.

Another aspect of the present invention relates to a method for preparing a titanium dioxide nanoparticle functionalized with an α-hydroxy alkanoic acid, comprising the step of: admixing a titanium dioxide nanoparticle with an α-hydroxy alkanoic acid to form a functionalized nanoparticle.

In certain instances, the present invention relates to the aforementioned method, wherein the temperature is in the range of about 50-100 ⁰C. In certain instances, the present invention relates to the aforementioned method, wherein said α-hydroxy alkanoic acid is an α-hydroxy (Ci-Ce)alkanoic acid.

In certain instances, the present invention relates to the aforementioned method, wherein said α-hydroxy alkanoic acid is lactic acid.

Another aspect of the present invention relates to a method for preparing a titanium dioxide nanoparticle functionalized with a silyl group, comprising the step of: admixing an N-(trialkoxysilylalkyl)dialkylene triamine with a l-hydroxy-2,3- epoxyalkyl group to form a silanating agent, and admixing said silanating agent with a titanium dioxide nanoparticle.

In certain instances, the present invention relates to the aforementioned method, wherein the temperature is in the range of about 50-100 ⁰C.

In certain instances, the present invention relates to the aforementioned method, wherein said N-(trialkoxysilylalkyl)dialkylene triamine is N,l-(3- trimethoxysilylpropyl)diethylene triamine.

In certain instances, the present invention relates to the aforementioned method, wherein said l-hydroxy-2,3-epoxyalkyl group is glycidol.

In certain instances, the present invention relates to the aforementioned method, wherein said N-(trialkoxysilylalkyl)dialkylene triamine is N,l-(3- trimethoxysilylpropyl)diethylene triamine, and said l-hydroxy-2,3-epoxyalkyl group is glycidol.

Nanoparticles of the Invention

One aspect of the present invention relates to a nanoparticle comprising a core coated with silica or functionalized with an organic compound, wherein said core comprises a metal, metal oxide, metal sulfide, zeolite, ceramic, diamond, carbon, protein, or a combination thereof.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide or ceramic.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core is coated with silica.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises ceramic, and said core is coated with silica.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core is ceramic, and said core is coated with silica. In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide, and said core is coated with silica.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide, and said core is functionalized with an α-hydroxy alkanoic acid. In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said core comprises titanium dioxide, and said core is functionalized with lactic acid. In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said nanoparticles have a sterility assurance level of at least about It)^"3.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said nanoparticles have a sterility assurance level of at least about

10 -5

Another aspect of the present invention relates to a stable nanoparticle that remains dispersed when placed in an aqueous solution, wherein the aqueous solution has a pH in the range of about 6.0 to about 8.0.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said nanoparticle remains dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

In certain embodiments, the present invention relates to the aforementioned nanoparticle, wherein said nanoparticle remains dispersed when placed in an aqueous solution having a pH of about 7.0.

Exemplification

The invention now being generally described, it will be more readily understood by reference to the following examples, which are included merely for purposes of illustration of certain aspects and embodiments of the present invention, and are not intended to limit the invention.

Example 1 Synthesis of 2-[(m-l,3-benzylidene glycerol)-2-propionic acid] - cw-l,3-O-Benzylidene glycerol (10.9 g, 60.4 mmol) was dissolved in 1,4-dioxane (250 mL) followed by the addition of NaH (7.0 g, 0.30 mol). The reaction mixture was stirred at rt for one hour before cooling to 0 ⁰C. 2-Bromopropionic acid (8.64 mL, 96 mmol) was then added over a 15 minute period of time. The reaction mixture was allowed to return to rt and then stirred at 50 ⁰C for 12 hours before it was cooled to 0 ⁰C and quenched with ethanol followed by the addition of water (250 mL). The solution was adjusted to 4.0 pH using IN HCl and extracted with CH₂Cl₂ (200 mL). This procedure was repeated once again after re-adjusting the pH to 4.0. The combined organic phase was dried with Na₂SO₄, gravity filtered, and evaporated. The solid was stirred in ethyl ether (50 mL) for 45 minutes and cooled to -25 ⁰C for 3 hours before collecting 11.7 g of the white powder (77.3 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.51 (d, 3, CH-CH₃, J=7.00 Hz), 3.46 (m, 1, -CH₂-CH-CH₂-, J=IJl Hz), 4.04 (m, 2, -CH₂-CH-CH^, J=I.71 Hz), 4.22 (q, 1, CH-CH₃, J= 7.00 Hz), 4.29 (m, 2, -CH₂- CH-CH₂;, J=Ul Hz), 5.54 (s, 1, CH), 7.34 (m, 3, arom. CHQ₁ 7.46 (m, 2, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 176.05 (COOH), 137.82 (CH), 129.34 (CH), 128.52 (CH), 126.26 (CH), 101.79 (CH), 72.83 (CH), 70.70 (CH), 69.28 (CH₂), 69.09 (CH₂), 18.79 (CH₃). FTIR: v (cm⁴) 1714 (C=O), 1455 (CH₂ bend), 1401 (CH₃ bend). GC-MS 253 m/z (MH⁺) (Theory: 252 m/z (M⁺)). GC-MS 253 m/z (MH⁺) (Theory: 252 m/z (M⁺)) Elemental Analysis C: 61.75 %; H 6.37 % (Theory: C: 61.90 %; H 6.39 %).

Example 2

Synthesis of benzylidene protected [G0]-PGLLA-bzld - 2-[(cώ-l,3-benzylidene glycerol)-2-propionic acid] (4.02 g, 15.9 mmol), cw-l,3-6>-benzylideneglycerol (2.62 g, 14.5 mmol), and DPTS (1.21 g, 4.10 mmol) were dissolved in CH₂Cl₂ (40 mL). The reaction flask was flushed with nitrogen and then DCC (3.61 g, 17.5 mmol) was added. Stirring at room temperature was continued for 14 hours under a nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of CH₂Cl₂ (10 mL) and the filtrate was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 MeOH:CH₂Cl₂. The product was dissolved in minimal CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Ethyl ether was decanted and the precipitate was exposed to reduced pressure to yield 5.63 g of a white powder (94.0 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.56 (d, 6, CH-CH₃, J=6.84 Hz), 3.47 (m, 2, -CH₂-CH-CH₂-, J=IJl Hz), 3.99 (m, 2, -CH₂-CH-CH₂=, J=Ul Hz), 4.14 (m, 2, -CH₂-CH-CH₂::, J=Ul Hz), 4.25 (m, 2, -CH₂- CH-CH₂-), 4.31 (m, 1, -CH₂-CH-CHa=), 4.37 (q, 1, CH-CH₃, J= 6.84 Hz), 4.42 (m, 1, -CH₂- CH-CH₂-), 4.72 (m, 1, -CH₂-CH-CH₂-, J=Ul Hz), 5.49 (s, 1, CH), 5.53 (s, 1, CH), 7.34 (m, 6, arom. CH)₁ 7.47 (m, 4, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 173.53 (COOR), 138.32 (CH), 137.97 (CH), 129.36 (CH), 129.10 (CH), 128.54 (CH), 128.40 (CH), 126.42 (CH), 126.20 (CH), 101.51 (CH), 101.46 (CH), 72.88 (CH), 70.80 (CH₂), 70.23 (CH), 69.08 (CH₂), 69.02 (CH₂), 68.19 (CH₂), 66.83 (CH), 19.34 (CH₃). FTIR: v (cm^"1) 1743 (C=O), 1452 (CH₂ bend), 1389 (CH₃ bend). GC-MS 415 m/z (MH⁺) (Theory: 414 m/z (M⁺)) Elemental Analysis C: 66.63 %; H 6.33 % (Theory C: 66.65 %; H 6.32 %).

Example 3

Synthesis of [GO]-PGLLA-OH - Pd/C (10%) (10 % w/w) was added to a solution of benzylidene protected [GO]-PGLLA (5.49 g, 13.2 mmol) in EtOAc/MeOH (3:1, 40 mL). The flask was evacuated and filled with 50 psi of H₂ before shaking for 20 minutes. The catalyst was filtered and washed with EtOAc (10 mL). The filtrate was then evaporated to give 2.94 g of a colorless, viscous oil (94.0 % yield). ¹H NMR (400 MHz, (CD₃)₂CO): δ 1.08 (m, 1, CH₃), 1.36 (m, 2, CH₃), 3.65 (broad m, 9, -CH₂-CH-CH₂-), 4.20 (broad m, 3, - CH₂-CH-CH₂-). ¹³C NMR (400 MHz, (CDs)₂SO): δ 174.03 (COOR), 81.53 (CH), 76.66 (CH), 74.30 (CH), 61.82 (CH₂), 61.69 (CH₂), 60.37 (CH₂), 19.62 (CH₃). FTIR: v (cml) 3383 (OH), 1737 (C=O). GC MS 239 m/z (MH⁺) (Theory: 238 m/z (M⁺)) Elemental Analysis C: 45.52 %; H 7.65 % (Theory C: 45.37 %; H 7.62%).

Example 4 Synthesis of benzylidene protected [Gl]-PGLLA-bzld - 2-[(cz,s'-l,3-benzylidene glycerol)-2-propionic acid] (4.41 g, 17.50 mmol), [GO]-PGLLA (0.791 g, 3.32 mmol), and DPTS (2.46 g, 8.36 mmol), were dissolved in DMF (80 mL). The reaction flask was flushed with nitrogen and then DCC (5.31 g, 25.74 mmol) was added. The contents were stirred at room temperature for 14 hours under nitrogen atmosphere. The DMF was removed under high vacuum and the remaining residue was dissolved in CH₂Cl₂. The DCC-urea was filtered and washed with a small amount of CH₂Cl₂ (20 mL) and the filtrate was concentrated. The crude product was purified by silica gel chromatography, eluting with 3:97 MeOH:CH₂Cl₂. The product was dissolved in minimal CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Ethyl ether was decanted and the precipitate was exposed to reduced pressure to yield 3.45 g of a white powder (88.3 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.33 (m, 3, CH₃), 1.47 (m, 12, CH₃), 3.41 (m, 4, CH,), 3.76 (m, 2, -CH₂-CH-CH₂-), 3.97 (m, 4, -CH₂-CH-CH₂-), 4.10 (m, 4, -CH₂-CH-CH₂-), 4.28 (m, 20, -CH₂-CH-CH₂-), 5.30 (m, 1, CH), 5.49 (m, 4, CH), 7.30 (m, 12, arom. CH), 7.46 (m, 8, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 173.16 (COOR), 138.24 (CH), 129.14 (CH), 128.40 (CH), 126.36 (CH), 101.47 (CH), 72.68 (CH), 70.54 (CH₂), 70.12 (CH), 68.13 (CH₂), 19.27 (CH₃), 18.99 (CH₃). FTIR: v cm-¹) 1745 (C=O), 1451 (CH₂ bend), 1386 (CH₃ bend). FAB MS 1175.6 m/z (MH⁺) (Theory: 1175.2 m/z (M⁺)) Elemental Analysis C: 62.11 %; H 6.46 % (Theory C: 62.34 %; H 6.35%). SEC M_w: 1280, M_n: 1260, PDI: 1.01.

Example 5

Synthesis of [Gl]-PGLLA-OH - Pd/C (10%) (10 % w/w) was added to a solution of benzylidene protected [Gl]-PGLLA (0.270 g, 0.230 mmol) in THF (15 mL). The flask was evacuated and filled with 50 psi of H₂ before shaking for 15 minutes. The catalyst was filtered and washed with THF (10 mL). The filtrate was then evaporated to give 0.178 g of a colorless, viscous oil (94.0 % yield). ¹H NMR (400 MHz, (CD₃)₂CO): δ 1.41 (m, 5, CH₃), 1.49 (m, 10, CH₃), 3.53 (m, 2, -CH₂-CH-CH₂-), 3.63 (m, 11, -CH₅-CH-CH₂-), 3.74 (m, 4, - CH₂-CH-CH₂-), 3.93 (m, 3, -CH₂-CH-CH₂-), 4.23 (m, 5, -CH₂-CH-CH₂-), 4.39 (m, 10, - CH₂-CH-CH₂-). ¹³C NMR (400 MHz, CD₃Cl): δ 169.64 (COOR), 74.53 (CH), 72.97 (CH), 72.74 (CH), 69.95 (CH₂), 68.97 (CH), 62.73 (CH₂), 61.76 (CH₂), 19.42 (CH₃), 18.13 (CH₃), 17.56 (CH₃). FTIR: v (cm^"1) 3409 (OH), 1733 (C=O), 1453 (CH₂ bend), 1374 (CH₃ bend). FAB MS 823.3 m/z (MH⁺) (Theory: 822.8 m/z (M⁺)) Elemental Analysis C: 47.72 %; H 7.41 % (Theory C: 48.17 %; H 7.11 %). SEC M_w: 1100, M_n: 1090, PDI: 1.01.

Example 6

Synthesis of benzylidene protected [G2]-PGLLA-bzld - 2-[(ciy-l,3-benzylidene glycerol)-2-propionic acid] (8.029 g, 31.83 mmol), DCC (9.140 g, 44.30 mmol), and DPTS (4.629 g, 15.74 mmol) were dissolved in THF (80 mL). The reaction flask was flushed with nitrogen and stirred for 30 minutes before [Gl]-PGLLA (0.825 g, 1.00 mmol) was added by dissolving in a minimal amount of THF. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. The DCC-urea was filtered and washed with a small amount of THF (20 mL). The THF filtrate was evaporated and the crude product was purified by silica gel chromatography, eluting with 3:97 MeOHiCH₂Cl₂. The product was dissolved in minimal CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Ethyl ether was decanted and the precipitate was exposed to reduced pressure to yield 2.09 g of a white powder (77 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.33 (m, 15, CH₃), 1.46 (m, 24, CH₃), 3.40 (m, 8, CH,), 3.77 (m, 5, -CH₂- CH-CH₂-), 3.95 (m, 10, -CH₂-CH-CH₂-), 4.06 (m, 12, -CH₂-CH-CH₂-), 4.28 (m, 47, -CH₂- CH-CH₂-), 5.49 (m, 8, CH), 7.30 (m, 24, arom. CH), 7.47 (m, 16, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 173.15 (COOR), 138.28 (CH), 129.12 (CH), 128.40 (CH), 126.36 (CH), 101.44 (CH), 72.69 (CH), 70.54 (CH₂), 70.12 (CH), 68.13 (CH₂), 19.23 (CH₃). FTIR: y cm^"1) 1746 (C=O), 1452 (CH₂ bend), 1386 (CH₃ bend). FAB MS 2697.0 m/z (MH⁺) (Theory: 2696.8 m/z (M⁺)) Elemental Analysis C: 60.86 %; H 6.37% (Theory C: 61.02 %; H 6.35 %). SEC M_w: 2350, M_n: 2310, PDI: 1.01.

Example 7 Synthesis of [G2]-PGLLA-OH - Pd/C (10%) (10 % w/w) was added to a solution of benzylidene protected [G2]-PGLLA (0.095 g, 0.035 mmol) in THF (10 niL). The flask was evacuated and filled with 50 psi of H₂ before shaking for 15 minutes. The catalyst was filtered and washed with THF (10 mL). The filtrate was evaporated to give 0.061 g of a colorless viscous oil (88.0 % yield). ¹H NMR (400 MHz, (CD₃)₂CO): δ 1.36 (m, 39, CH₃), 3.61 (m, 48, -CH₂-CH-CH₂-), 3.94 (m, 10, -CH₂-CH-CH₂-), 4.16 (m, 6, -CH₂-CH-CH₂-), 4.35 (m, 29, -CH₂-CH-CH₂-). ¹³C NMR (400 MHz, (CD₃)₂CO): δ 174.37 (COOR), 81.98 (CH), 74.16 (CH), 70.46 (CH), 62.32 (CH₂), 62.09 (CH₂), 18.76 (CH₃). FTIR: v (cm^"1) 3431 (OH), 1741 (C=O), 1453 (CH₂ bend), 1376 (CH₃ bend). MALDI-TOF MS 1991.8 m/z (MH⁺) (Theory: 1991.9m/z (M⁺)). SEC M_w: 2170, M_n: 2130, PDI: 1.01.

Example 8

Synthesis of [G2]-PGLLA-Ac - [G2J-PGLLA (0.098 g, 0.049 mmol) was dissolved in 5 mL of pyridine. Acetic anhydride (6.0 mL, 64 mmol) was then added via syringe and the reaction mixture was stirred at 40 ⁰C for 8 hours. Pyridine and acetic anhydride were removed under high vacuum. The product was isolated on a prep TLC eluting with 4:96 MeOH: CH₃Cl. ¹H NMR (400 MHz, CD₃Cl): δ 1.22 (m, 15, CH₃), 1.39 (m, 24, CH₃), 2.05 (m, 48, CH₃), 3.62 - 4.21 (broad multiplets, 83, -CH₂-CH-CH₂-). ¹³C NMR (400 MHz, CD₃Cl): δ 172.69 (COOR), 170.87 (COOR), 75.15 (CH), 74.60 (CH), 70.46 (CH), 63.68 (CH₂), 63.17 (CH₂), 29.88 (CH₃), 21.02 (CH₃), 19.01 (CH₃). FAB MS 2665.0 m/z (MH⁺) (Theory: 2664.5 m/z (M⁺)) Elemental Analysis C: 50.70 %; H 6.71 % (Theory C: 50.94 %; H 6.43 %).

Example 9

Synthesis of benzylidene protected [G3]-PGLLA-bzId - 2-[(cώ-l,3-benzylidene glycerol)-2-propionic acid] (0.376 g, 1.49 mmol), DCC (0.463 g, 2.24 mmol), and DPTS (0.200 g, 0.680 mmol) were dissolved in THF (15 mL). The reaction flask was flushed with nitrogen and stirred for 1.5 hours before [G2]-PGLLA (0.070 g, 0.035 mmol) was added by dissolving in a minimal amount of THF. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. The DCC-urea was filtered and washed with a small amount of THF (20 mL). The THF filtrate was evaporated and the crude product was purified by silica gel chromatography, eluting with 3:97 MeOH:CH₂Cl₂. The product was dissolved in minimal CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Ethyl ether was decanted and the precipitate was exposed to reduced pressure to yield 0.164 g of a white powder (89.1 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.32 (m, 39, CH₃), 1.45 (m, 48, CH₃), 3.38 (m, 16, CH,), 3.77 (m, 14, -CH₂-CH-CH₂-), 3.97 (m, 20, -CH₂-CH-CH₂-), 4.07 (m, 24, -CH₂-CH-CH₂-), 4.24 (m, 97, - CH₂-CH-CH₂-), 4.39 (m, 8, -CH₂-CH-CH₂-), 5.47 (m, 16, CH), 7.31 (m, 48, arom. CH), 7.44 (m, 32, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 173.14 (COOR)₅ 138.28 (CH), 129.12 (CH), 128.40 (CH), 126.36 (CH), 101.41 (CH), 72.68 (CH), 70.56 (CH₂), 70.13 (CH), 68.11 (CH₂), 19.25 (CH₃), 19.02 (CH₃). FTIR: y cm^"1) 1744 (C=O), 1451 (CH₂ bend), 1385 (CH₃ bend). MALDI MS 5743.3 m/z (MH⁺) (Theory: 5739.9 m/z (M⁺)) Elemental Analysis C: 60.32 %; H 6.34% (Theory C: 60.47 %; H 6.36 %). SEC M_w: 4370, M_n: 4310, PDI: 1.01.

Example 10

Synthesis of [G3]-PGLLA-OH - Pd/C (10%) (10 % w/w) was added to a solution of benzylidene protected [G3J-PGLLA (0.095 g, 0.035 mmol) in THF (15 mL). The flask was evacuated and filled with 50 psi of H₂ before shaking for 15 minutes. The catalyst was filtered and washed with THF (10 mL). The filtrate was evaporated to give 0.128 g of a colorless viscous oil (95.4 % yield). ¹H NMR (400 MHz, (CD₃)₂CO): δ 1.37 (m, 87, CH₃), 3.56 (m, 83, -CH₂-CH-CH₂- or -CH-CH₃), 3.78 (m, 13, -CH₂-CH-CH₂- or -CH-CH₃), 4.01 (m, 14, -CH₂-CH-CH₂- or -CH-CH₃), 4.18 (m, 13, -CH₂-CH-CH₂- or -CH-CH₃), 4.39 (m, 56, -CH₂-CH-CH₂- or -CH-CH₃). ¹³C NMR (400 MHz, (CD₃)₂CO): δ 174.37 (COOR), 82.01 (CH), 74.16 (CH), 62.35 (CH₂), 62.15 (CH₂), 18.80 (CH₃). FTIR: v (cm-¹) 3434 (OH), 1738 (C=O), 1452 (CH₂ bend), 1376 (CH₃ bend). MALDI MS 4332.5 m/z (MH⁺) (Theory: 4330.2 m/z (M⁺)) Elemental Analysis C: 49.56 %; H 7.21 % (Theory C: 49.09 %; H 6.94%). SEC M_w: 4110, M_n: 4060, PDI: 1.01.

Example 11 Synthesis of [G0]-PGLSA-bzld - Succinic acid (1.57 g, 13.3 mmol), cis-l,3-O- benzylideneglycerol (5.05 g, 28.0 mmol), and DPTS (4.07 g, 13.8 mmol) were dissolved in CH₂Cl₂ (120 mL). The reaction flask was flushed with nitrogen and then DCC (8.19 g, 39.7 mmol) was added. Stirring at room temperature was continued for 14 hours under a nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of CH2CI₂ (20 mL). The crude product was purified by silica gel chromatography, eluting with 3:97 methanol: CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Following vacuum filtration, 5.28 g of a white solid was collected (90 % yield). ¹H NMR (CDCl₃): δ 2.78 (s, 4, -CH₁-CH₂-), 4.08 (m, 4, -CH₂-CH-CH₂-), 4.23 (m, 4, -CH₂-CH- CH₂-), 4.69 (m, 2, -CH₂-CH-CH₂-, J=1.54 Hz, 1.71 Hz), 5.50 (s, 2, CH), 7.34 (m, 6, arom. CH), 7.48 (m, 4, arom. CH). ¹³C NMR (CDCl₃): δ 172.32 (COOR), 138.03 (CH), 129.23 (CH), 128.48 (CH), 126.24 (CH), 101.33 (CH), 69.16 (CH₂), 66.50 (CH), 29.57 (CH₂). FTIR: v (cm⁴) 2992 (aliph. C-H stretch), 1727 (C=O). GC-MS 443 m/z (MH⁺) (Theory: 442 m/z (M⁺)). HR FAB 442.1635 m/z (M⁺) (Theory: 442.1628 m/z (M⁺)). Elemental Analysis C: 65.25 %; H 5.85 % (Theory C: 65.15 %; H 5.92 %).

Example 12 Synthesis of [GO]-PGLSA-OH - Pd/C (10 % w/w) was added to a solution of benzylidene protected [GO]-PGLSA (2.04 g, 4.61 mmol) in THF (30 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 50 psi OfH₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (20 mL). The filtrate was evaporated to give 1.18 g of a clear viscous oil (97 % yield). ¹H NMR (CD₃OD): δ 2.67 (s, 4, -CBb-CH₂-), 3.64 (m, 8, -CH₂-CH-CH₂-), 4.87 (m, 2, -CH₂-CH-CH₂-). ¹³C NMR (CD₃OD): δ 172.77 (COOR), 75.84 (CH₂), 60.41 (CH), 28.96 (CH₂). ¹³C NMR ((CD₃)₂CO): δ 171.99 (COOR), 76.15 (CH₂), 60.89 (CH). FTIR: v (cm^"1) 3299 (OH), 1728 (C=O). GC-MS 284 m/z (M+NHUt) (Theory: 266 m/z (M⁺)). Elemental Analysis C: 44.94 %; H 6.87 % (Theory C: 45.11 %; H 6.81%).

Example 13

Synthesis of 2-(cis-l,3-(?-benzylidene glycerol)succinic acid mono ester - cis-l,3-O- Benzylideneglycerol (9.90 g, 54.9 mmol) was dissolved in pyridine (100 mL) followed by the addition of succinic anhydride (8.35 g, 83.4 mmol). The reaction mixture was stirred at room temperature for 18 hours before the pyridine was removed under vacuum at 40 ⁰C. The remaining solid was dissolved in CH₂Cl₂ (100 mL) and washed three times with cold 0.2 N HCl (100 mL), or until the aqueous phase remained at pH 1. The organic phase was evaporated and the solid was dissolved in deionized water (300 mL). 1 N NaOH was added until pH 7 was obtained and the product was dissolved in solution. The aqueous phase was extracted with CH₂Cl₂ (200 niL) and then readjusted to pH 4. The aqueous phase was subsequently extracted twice with CH₂Cl₂ (200 mL), dried with Na₂SO₄, filtered, and evaporated. The solid was stirred in ethyl ether (50 mL) and cooled to -25 ⁰C for 3 hours before collecting 14.6 g of a white powder (95 % yield). ¹H NMR (CDCl₃): δ 2.68 (m, 4, - CH₂-CH₂-), 4.13 (m, 2, -CH₂-CH-CH₂-), 4.33 (m, 2, -CH₂-CH-CH₂-), 4.70 (m, 1, -CH₂-CH- CH₂-), 5.51 (s, 1, CH), 7.34 (m, 3, arom. CH), 7.47 (m, 2, arom. CH). ¹³C NMR (CDCl₃): δ 178.07 (COOH), 172.38 (COOR), 137.95 (CH), 129.33 (CH), 128.51 (CH), 126.26 (CH), 101.43 (CH), 69.15 (CH₂), 66.57 (CH), 29.24 (CH₂), 29.05 (CH₂). FTIR: v (cm^"1) 2931 (aliph. C-H stretch), 1713 (C=O). GC-MS 281 m/z (MH⁺) (Theory: 280 m/z (M⁺)). Elemental Analysis C: 60.07 %; H 5.80 % (Theory: C: 59.99 %; H 5.75 %).

Example 14

Synthesis of [Gl]-PGLSA-bzld - 2-(cw-l,3-<9-Benzylidene glycerol)succinic acid mono ester (6.33 g, 22.6 mmol), [GO]-PGLSA (1.07 g, 4.02 mmol), and DPTS (2.51 g, 8.53 mmol) were dissolved in THF (60 mL). The reaction flask was flushed with nitrogen and then DCC (7.04 g, 34.1 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 to 5:95 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was isolated to yield 5.11 g of a white powder (97 % yield). ¹H NMR (CDCl₃): δ 2.58 (m, 4, -CH₂-CH₂-), 2.63 (m, 8, -CH₂-CII₂-), 2.71 (m, 8, -CH₂-CH₂-), 4.12 (m, 12, -CH₂-CH-CH₂-), 4.23 (m, 12, -CH₂-CH-CH₂-), 4.69 (m, 4, -CH₂-CH-CH₂-), 5.20 (m, 2, -CH₂-CH-CH₂-), 5.51 (m, 4, CH), 7.33 (m, 12, arom. CH), 7.46 (m, 8, arom. CH). ¹³C NMR (CDCl₃): δ 172.28 (COOR), 171.91 (COOR), 171.53 (COOR), 138.03 (CH), 129.26 (CH), 128.48 (CH), 126.22 (CH), 101.32 (CH), 69.50 (CH)₅ 69.16 (CH₂), 66.54 (CH), 62.49 (CH₂), 29.36 (CH₂), 29.03 (CH₂). FTIR: v (cin ¹) 2858 (aliph. C-H stretch), 1731 (C=O). FAB MS 1315.6 m/z (MH⁺) (Theory: 1315.3 m/z (M⁺)). Elemental Analysis C: 60.13 %; H 5.82 % (Theory C: 60.27 %; H 5.67%). SEC M_w: 1460, M_n: 1450, PDI: 1.01. Example IS

Synthesis of [Gl]-PGLSA-OH - Pd/C (10 % w/w) was added to a solution of benzylidene protected [Gl]-PGLSA (0.270 g, 0.230 mmol) in THF (20 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 50 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (20 mL). The filtrate was evaporated to give

0.178 g of a colorless, viscous oil (94 % yield). ¹H NMR (CD₃OD): δ 2.63 (m, 20, -CH₂-

CH₂-), 3.52 (m, 4, -CH₂-CH-CH₂-), 3.64 (m, 8, -CH₂-CH-CH₂-), 3.80 (ra, 2, -CH₂-CH-CH₂-

), 4.05 (m, 2, -CH₂-CH-CH₂-), 4.14 (m, 2, -CH₂-CH-CH₂-), 4.21 (m, 4, -CH₂-CH-CH₂-),

4.30 (m, 4, -CH₂-CH-CH₂-), 4.85 (m, 2, -CH₂-CH-CH₂-), 5.25 (m, 2, -CH₂-CH-CH₂-). ¹³C NMR (CD₃OD): δ 172.82 (COOR), 172.58 (COOR), 172.48 (COOR), 172.08 (COOR),

75.82 (CH), 69.90 (CH), 69.68 (CH), 65.66 (CH₂), 62.85 (CH₂), 62.30 (CH₂), 60.43 (CH₂),

28.83 (CH₂), 28.61 (CH₂). FTIR: v (cm^"1) 3405 (OH), 2943 (aliph. C-H stretch), 1726 (C=O). FAB MS 963.2 m/z (MH⁺) (Theory: 962.9 m/z (M⁺)). Elemental Analysis C: 47.13 %; H 6.11 % (Theory C: 47.40 %; H 6.07 %). SEC M_w: 1510, M_n: 1500, PDI: 1.01.

Example 16

Synthesis of [G2]-PGLSA-bzld - 2-(cώ-l,3-0-Benzylidene glycerol)succinic acid mono ester (4.72 g, 16.84 mmol), [Gl]-PGLSA (1.34 g, 1.39 mmol), and DPTS (1.77 g, 6.02 mmol) were dissolved in THF (100 mL). The reaction flask was flushed with nitrogen and then DCC (4.62 g, 22.4 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 to 5:95 methanol: CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was isolated to yield 4.00 g of a white powder (94 % yield). ¹H NMR (CDCl₃): δ 2.59 (broad m, 26, -CH₂-CH₂-), 2.69 (broad m, 52, -CH₂-CH₂-), 4.13 (m, 28, -CH₂-CH-CH₂-), 4.13 (m, 28, -CH₂-CH-CH₂-), 4.69 (m, 8, -CH₂-CH-CH₂-), 5.22 (m, 6, -CH₂-CH-CH₂-), 5.50 (s, 8, CH), 7.32 (m, 24, arom. CH), 7.47 (m, 16, arom. CH). ¹³C NMR (CDCl₃): δ 172.27 (COOR), 171.88 (COOR), 171.60 (COOR), 138.04 (CH), 129.25 (CH), 128.47 (CH), 126.21 (CH), 101.30 (CH), 69.48 (CH), 69.15 (CH₂), 66.54 (CH), 62.57 (CH₂), 29.35 (CH₂), 29.18 (CH₂) 29.03 (CH₂), 28.84 (CH₂). FTIR: ycm^"1) 2969 (aliph. C-H stretch), 1733 (C=O). FAB MS 3060.7 m/z (MH⁺) (Theory: 3060.9 m/z (M⁺)). Elemental Analysis C: 59.20 %; H 5.64 % (Theory C: 58.86 %; H 5.60 %). SEC M_w: 3030, M_n: 2990, PDI: 1.01.

Example 17

Synthesis of [G2]-PGLSA-OH - Pd/C (10 % w/w) was added to a solution of benzylidene protected [G2]-PGLSA (2.04 g, 0.667 mmol) in THF (20 niL). The flask for catalytic hydrogenolysis was evacuated and filled with 50 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (20 niL). The filtrate was evaporated to give 1.49 g of a colorless, viscous oil (95 % yield). ¹H NMR (CD₃OD): δ 2.64 (m, 52, -CH₂- CH₂-), 3.53 (m, 16, -CH₂-CH-CH₂-), 3.64 (m, 4, -CH₂-CH-CH₂-), 3.80 (m, 8, -CH₂-CH- CH₂-), 4.06 (m, 8, -CH₂-CH-CH₂-), 4.14 (m, 6, -CH₂-CH-CH₂-), 4.21 (m, 11, -CH₂-CH- CH₂-), 4.30 (m, 11, -CH₂-CH-CH₂-), 5.25 (m, 6, -CH₂-CH-CH₂-). ¹³C NMR (CD₃OD): δ 172.83 (COOR), 172.59 (COOR), 172.49 (COOR), 69.91 (CH), 69.69 (CH), 65.68 (CH₂), 62.88 (CH₂), 62.37 (CH₂), 28.61 (CH₂). FTIR: v (cnf¹) 3429 (OH), 2952 (aliph. C-H stretch), 1728 (C=O). MALDI MS 2357.3 m/z (MH⁺) (Theory: 2356.1 m/z (M⁺)). Elemental Analysis C: 48.32 %; H 5.97 % (Theory C: 47.92 %; H 5.90%). SEC M_w: 3060, M_n: 3000, PDI: 1.02.

Example 18

Synthesis of succinic acid monomethallyl ester (SAME) - 2-Methyl-2-propen-l-ol (4.90 mL, 58.2 mmol) was dissolved in pyridine (20 mL) followed by the addition of succinic anhydride (7.15 g, 71.4 mmol). The reaction mixture was stirred at room temperature for 15 hours before the pyridine was removed under vacuum at 30 ⁰C. The remaining liquid was dissolved in CH₂Cl₂ (100 mL) and washed two times with cold 0.2 N HCl (100 mL). The organic phase was dried with Na₂SO₄, gravity filtered, and evaporated to give 9.25 g of a clear liquid (92 % yield). ¹H NMR (CDCl₃): δ 1.70 (s, 3, CH₃), 2.64 (m, 4, -CH₅-CH₂-), 4.48 (s, 2, -CH₂-), 4.88 (m, 1, vinyl CH₂), 4.93 (m, 1, vinyl CH₂). ¹³C NMR (CDCl₃): δ 178.58 (COOH), 172.05 (COOR), 139.88 (CH), 113.31 (CH₂), 68.31 (CH₂), 29.11 (CH₂), 28.99 (CH₂), 19.59 (CH₃). FTIR: v (cmf¹) 2939 (aliph. C-H stretch), 1711 (C=O). GC-MS 173 m/z (MH⁺) (Theory: 172 m/z (M⁺)). Elemental Analysis C: 55.51 %; H 7.09 % (Theory: C: 55.81 %; H 7.02 %). Example 19

Synthesis of [G2] -PGLSA-SAME - Succinic acid monomethallyl ester (0.826 g, 4.80 mmol), [G2]-PGLSA (0.401 g, 0.170 mmol), and DPTS (0.712 g, 2.42 mmol) were dissolved in THF (50 mL). The reaction flask was flushed with nitrogen and then DCC (1.52 g, 7.37 mmol) was added. Stirring at room temperature was continued for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of CH₂Cl₂ (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 to 5:95 methanol: CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was isolated to yield 0.558 g of a clear colorless oil (68.2 % yield). ¹H NMR (CDCl₃): δ 1.72 (s, 48, CH₃), 2.63 (m, 116, -CH₂-CH₂-), 4.16 (m, 23, -CH₂-CH-CH₂-), 4.27 (m, 23, - CH₂-CH-CH₂-), 4.48 (s, 32, -CH₂-), 4.89 (s, 16, vinyl CH₂), 4.94 (s, 16, vinyl CH₂), 5.24 (m, 14, -CH₂-CH-CH₂-). ¹³C NMR (CDCl₃): δ 171.91 (COOR), 171.67 (COOR), 139.98 (CH), 113.22 (CH₂), 69.43 (CH), 68.31 (CH₂), 62.56 (CH₂), 29.10 (CH₂), 29.02 (CH₂) 28.83 (CH₂), 19.66 (CH₃). FTIR: v (χm^-1) 2969 (aliph. C-H stretch), 1734 (C=O). MALDI MS 4840.9 m/z (MH⁺) (Theory: 4838.7 m/z (M⁺)). Elemental Analysis C: 55.37 %; H 6.22 % (Theory C: 55.35%; H 6.29%). SEC M_w: 5310, M_n: 5230, PDI: 1.02.

Example 20 Synthesis of [G3]-PGLSA-bzld - 2-(cώ-l,3-0-Benzylidene glycerol)succinic acid mono ester (2.77 g, 9.89 mmol), [G2]-PGLSA (1.00 g, 0.425 mmol), and DPTS (1.30 g, 4.42 mmol) were dissolved in THF (40 mL). The reaction flask was flushed with nitrogen and then DCC (2.67 g, 12.9 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 to 5:95 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was isolated to yield 3.51 g of a white powder (90 % yield). ¹H NMR (CDCl₃): δ 2.57 - 2.72 (broad m, 116, -CH₂-CH₂-), 4.12 (m, 60, -CH₂-CH-CH₂-), 4.23 (m, 60, -CH₂-CH-CH₂-), 4.68 (m, 16, -CH₂-CH-CH₂-), 5.22 (m, 14, -CH₂-CH-CH₂-), 5.49 (s, 16, CH), 7.33 (m, 48, arom. CH), 7.46 (m, 32, arom. CH). ¹³C NMR (CDCl₃): δ 172.31 (COOR), 171.97 (COOR), 171.65 (COOR), 138.01 (CH), 129.28 (CH), 128.49 (CH), 126.21 (CH), 101.28 (CH), 69.45 (CH), 69.16 (CH₂), 66.53 (CH), 62.59 (CH₂), 29.32 (CH₂), 29.16 (CH₂) 29.01 (CH₂), 28.81 (CH₂). FTIR: ycm^"1) 2984 (aliph. C-H stretch), 1733 (C=O). MALDI MS 6553.4 m/z (MH⁺) (Theory: 6552.2 m/z (M⁺)). Elemental Analysis C: 58.50 %; H 5.66 % (Theory C: 58.29 %; H 5.57 %). SEC M_w: 5550, M_n: 5480, PDI: 1.01.

Example 21

Synthesis of [G3]-PGLSA-OH - Pd/C (10 % w/w) was added to a solution of benzylidene protected [G3]-PGLSA (1.23 g, 0.188 mmol) in 9:1 THF/MeOH (20 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 50 psi Of H₂ before shaking for 10 hours. The catalyst was filtered and washed with 9:1 THF/MeOH (20 mL). The filtrate was evaporated to give 0.923 g of a colorless, viscous oil (95 % yield). ¹H NMR (CD₃OD): δ 2.64 (m, 116, -CH₂-CH₂-), 3.51 (m, 26, -CH₂-CH-CH₂-), 3.67 (m, 28, -CH₂-CH-CH₂-), 3.80 (m, 12, -CH₂-CH-CH₂-), 4.05 (m, 14, -CH₂-CH-CH₂-), 4.14 (m, 14, -CH₂-CH-CH₂-), 4.22 (m, 22, -CHb-CH-CH₂-), 4.30 (m, 22, -CH₂-CH-CH₂-), 5.26 (m, 14, -CH₂-CH-CH₂). ¹³C NMR (CD₃OD): δ 172.86 (COOR), 69.91 (CH), 67.64 (CH), 65.67 (CH₂), 62.87 (CH₂), 62.41 (CH₂), 28.61 (CH₂). FTIR: v (cm^"1) 3442 (OH), 2959 (aliph. C-H stretch), 1731 (C=O). MALDI MS 5144.8 m/z (MH⁺) (Theory: 5142.5 m/z (M⁺)). Elemental Analysis C: 48.07 %; H 5.84 % (Theory C: 48.11 %; H 5.84 %). SEC M_w: 5440, M_n: 5370, PDI: 1.01. Example 22

Synthesis of [G4]-PGLSA-bzId - 2-(c/.s-l,3-<9-Benzylidene glycerol)succinic acid mono ester (2.43 g, 8.67 mmol), [G3]-PGLSA (0.787 g, 0.153 mmol), and DPTS (1.30 g, 4.42 mmol) were dissolved in 10:1 THF/DMF (40 mL). The reaction flask was flushed with nitrogen and then DCC (2.63 g, 12.7 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, solvents were removed under vacuum and the remaining solids were redissolved CH₂Cl₂. The DCC-urea was filtered and washed with a small amount of CH₂Cl₂ (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 to 5:95 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was exposed to reduced pressure to yield 1.5O g of a white powder (73 % yield). ¹H NMR (CDCl₃): δ 2.63 (m, 70, -CH₂-CH₂-), 2.72 (m, 146, -CH₂- CH₂-), 2.90 (m, 32, -CH₂-CHb-), 4.14 (m, 100, -CH₂-CH-CH₂-), 4.25 (m, 100, -CH₂-CH- CH₂-), 4.70 (m, 32, -CH₂-CH-CH₂-), 5.25 (m, 16, -CH₂-CH-CH₂-), 5.52 (s, 32, CH), 7.33 (m, 96, arom. CH), 7.47 (m, 64, arom. CH). ¹³C NMR (CDCl₃): δ 172.27 (COOR), 171.90 (COOR), 171.57 (COOR), 138.08 (CH), 129.25 (CH), 128.47 (CH), 126.23 (CH), 101.27 (CH), 69.49 (CH), 69.13 (CH₂), 66.54 (CH), 62.45 (CH₂), 29.34 (CH₂), 29.02 (CH₂), 28.83 (CH₂). FTIR: v (χnf¹) 2978 (aliph. C-H stretch), 1733 (C=O). MALDI MS 13536.8 m/z (MH⁺) (Theory: 13534.7 m/z (M⁺)). Elemental Analysis C: 58.20 %; H 5.56 % (Theory C: 58.04 %; H 5.56 %). SEC M_w: 9000, M_n: 8900, PDI: 1.01.

Example 23 Synthesis of [G4J-PGLSA-OH - Pd/C (10 % w/w) was added to a solution of benzylidene protected [G4J-PGLSA (0.477 g, 0.0352 mmol) in 9:1 THF/MeOH (20 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 50 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with 9:1 THF/MeOH (20 mL). The filtrate was evaporated to give 0.351 g of a colorless, viscous oil (93 % yield). ¹H NMR (CD₃OD): δ 2.65 (m, 244, -CB₂-CB₂-), 3.53 (m, 50, -CH₂-CH-CH₂), 3.65 (m, 22, -CH₂-CH-CH₂-), 3.81 (m, 28, -CH₂-CH-CH₂-), 4.05 (m, 32, -CH₂-CH-CH₂-), 4.14 (m, 32, -CHb-CH-CH₂-), 4.24 (m, 60, -CH₂-CH-CH₂-), 4.30 (m, 60, -CH₂-CH-CH₂-), 5.26 (m, 32, -CH₂-CH-CH₂-). ¹³C NMR (CD₃OD): δ 172.94 (COOR), 69.92 (CH), 65.72 (CH₂), 62.91 (CH₂), 28.67 (CH₂). FTIR: v (cm-¹) 3444 (OH), 2931 (aliph. C-H stretch), 1729 (C=O). MALDI MS 10715.6 m/z (MH⁺) (Theory: 10715.3 m/z (M⁺)). Elemental Analysis C: 48.50 %; H 5.83 % (Theory C: 48.20 %; H 5.81 %). SEC M_w: 8800, M_n: 8720, PDI: 1.01.

Example 24

The PGLSA dendrimers or other dendrimers described herein can also be synthesized through Accelerated Syntheses for example: Example 24.1 Synthesis of 2-(cis-l,3-O-benzyIidene glycerol)succinic acid mono ester anhydride - 2-(cw-l,3-O-Benzylidene glycerol)succinic acid mono ester (50.00 g, 178.4 mmol) ) and DCC (22.09 g, 107.0 mmol) were dissolved in DCM (300 mL) and stirred for 14 hours. The DCU precipitate was collected by filtration and washed with DCM (50 mL). The organic phase was directly added to 900 mL of hexanes. The hexanes and precipitate were cooled to -20 ⁰C for 3 hours before 46.11 g of precipitate was collected after filtration (95 % yield). ¹H NMR (CDCl₃): δ 2.75 (m, 4, -CH₂-CH₂-), 4.12 (m, 4, -CH₂-CH-CH₁-), 4.25 (m, 4, -CH₂-CH-CH₂-), 4.71 (m, 2, -CH₂-CH-CH₂-), 5.52 (s, 2, CH), 7.34 (m, 6, arom. CH)₅ 7.47 (m, 4, arom. CH). ¹³C NMR (CDCl₃): δ 171.77 (COOR), 167.99 (-COOCO-), 137.96 (CH), 129.29 (CH)₅ 128.51 (CH)₅ 126.20 (CH)₅ 101.36 (CH), 69.13 (CH₂), 66.76 (CH)₅ 30.37 (CH₂), 28.94 (CH₂). FTIR: v (cm^"1) 2938 (aliph. C-H stretch), 1815 (C=O), 1730 (C=O). FAB-MS 543.2 m/z [M-H]⁺ (Theory: 542.53 m/z [M]⁺). Elemental Analysis C: 61.83 %; H 5.70 % (Theory: C: 61.99 %; H 5.57 %).

Example 24.2 Synthesis of [Gl]-PGLSA-bzld .- Pd(OH)₂/C (10% w/w) and activated carbon were added to a solution of [GO]-PGLSA-bzld (3.571 g, 8.071 mmol) in THF (25 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst and activated carbon were filtered off and washed with THF (50 mL). 2-(cw-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (21.990 g, 40.532 mmol) and then DMAP (0.514 g, 4.207 mmol) were directly added to the deprotected core in the THF ( more THF was added to give a total volume of 100 mL). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Any remaining anhydride was quenched by the addition of n-propanol (4.0 mL, 44 mmol), which was allowed to stir for another 5 hours. The THF was removed under vacuum and the remaining contents were dissolved in DCM (250 mL) and washed once with 0.1 N HCl (200 mL) and three times with saturated sodium bicarbonate (200 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the dendrimer was precipitated in hexanes (450 mL) and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 10.29 g of a white solid (96.9 % yield). ¹H NMR, ¹³C NMR, FTIR, MALDI-TOF MS₅ Elemental Analysis, and SEC have been previously reported. T_g (⁰C): 36.7 to 42.4, 39.5 at half-height.

Example 24.3 Synthesis of [G2]-PGLSA-bzld (186) - Pd(OH)₂/C (10% w/w) and activated carbon were added to a solution of [Gl] -PGLS A-bzld (4.40 g, 3.43 mmol) in THF (50 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst and activated carbon were filtered off and washed with THF (50 mL). 2-(cw-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (18.459 g, 34.024 mmol) and then DMAP (0.831 g, 6.802 mmol) were directly added to the deprotected dendrimer in the THF. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Any remaining anhydride was quenched by the addition of n-propanol (3.0 mL, 33 mmol), which was allowed to stir for another 5 hours. The THF was removed under vacuum and the remaining contents were dissolved in DCM (400 mL) and washed once with 0.1 N HCl (300 mL) and three times with saturated sodium bicarbonate (300 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the dendrimer was precipitated in hexanes (900 mL) and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 9.85 g of a white solid (96.2 % yield). ¹H NMR, ¹³C NMR, FTIR, MALDI-TOF MS, Elemental Analysis, and SEC have been previously reported. T_g (⁰C): 39.3 to 45.4, 42.3 at half-height.

Example 24.4 Synthesis of [G3]-PGLSA-bzId - Pd(OH)₂/C (10% w/w) and activated carbon were added to a solution of [G2]-PGLSA-bzld (12.81 g, 4.218 mmol) in THF (100 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst and activated carbon were filtered off and washed with THF (100 mL). From this solution, 1.822 g of [G2J-PGLSA-OH in THF was removed form the mixture. Next, 2-(cώ-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (45.9154 g, 84.632 mmol) and then DMAP (1.5592 g, 12.763 mmol) were directly added to the deprotected core in the THF. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Any remaining anhydride was quenched by the addition of n-propanol (8.0 mL, 88 mmol), which was allowed to stir for another 5 hours. The THF was removed under vacuum and the remaining contents were dissolved in DCM (500 mL) and washed once with 0.1 N HCl (400 mL) and three times with saturated sodium bicarbonate (400 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the dendrimer was precipitated in hexanes (800 mL) and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 20.37 g of a white solid (91.4 % yield). ¹H NMR, ¹³C NMR, FTIR, MALDI-TOF MS, Elemental Analysis, and SEC have been previously reported. T_g (⁰C): 43.1 to 48.3, 45.7 at half-height. Example 24.5 Synthesis of [G3J-PGLSA-OH - Pd(OH)₂/C (10% w/w) and activated carbon were added to a solution of [G3]-PGLSA-bzld (3.571 g, 8.071 mmol) in THF/MeOH (9:1) (25 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi Of H₂ before shaking for 10 hours. The catalyst and activated carbon were filtered off and washed with more of the THF/MeOH solution (50 mL) before the solvents were evaporated. The product was used directly in next reaction Example 24.6 Synthesis of [G4]-PGLSA-bzId - The deprotected core was dissolved in the THF/dimethyl acetimide (10:1) (200 mL) and 2-(cώ-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (60.83 g, 0.11212 mmol) and then DMAP (1.63 g, 13.342 mmol) were directly added to the reaction flask. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Any remaining anhydride was quenched by the addition of n-propanol (4.0 mL, 44 mmol), which was allowed to stir for another 5 hours. The solvents were removed under vacuum and the remaining contents were dissolved in DCM (250 mL) and washed once with 0.1 N HCl (200 mL) and three times with saturated sodium bicarbonate (200 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the dendrimer was precipitated in hexanes (450 mL) and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 33.25 g of a white solid (88.15 % yield). ¹H NMR, ¹³C NMR, FTIR, MALDI-TOF MS, Elemental Analysis, and SEC have been previously reported. T_g (⁰C): 43.6 to 49.6, 47.0 at half-height.

Example 24.7 Synthesis of [G5]-PGLSA-bzld - [G4]-PGLSA-OH (0.2052 g, 0.0192 mmol) and 2-(cώ-l,3-(9-Benzylidene glycerol)succinic acid mono ester anhydride (0.067 g, 0.548 mmol), were dissolved in 1: 1 THF/DMF (15 mL). DMAP (1.152 g, 2.123 mmol) was added and the reaction flask was flushed with nitrogen. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Any remaining anhydride was quenched by the addition of water (4.0 mL) which was allowed to stir for another 5 hours. The solvents were removed under vacuum and the remaining contents were dissolved in DCM (150 mL) and washed once with 0.1 N HCl (100 mL) and three times with saturated sodium bicarbonate (100 mL). The organic phase was dried with Na₂Sθ₄, filtered, and concentrated before the dendrimer was precipitated in hexanes (450 mL) and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 0.414 g of a white solid (78.6 % yield). ¹H NMR (CDCl₃): δ 2.57-2.69 (broad m, 488, -CH₂-CH₂-), 4.07-4.21 (m, 507, -CH₂-CH-CH₂-), 4.66 (m, 64, -CH₂-CH-CH₂-), 5.19 (m, 63, -CH₂-CH- CH₂-), 5.48 (s, 64, CH), 7.31 (m, 194, arom. CH), 7.44 (m, 128, arom. CH). ¹³C NMR (CDCl₃): δ 172.28 (COOR), 171.91 (COOR), 171.61 (COOR), 138.08 (CH), 129.25 (CH), 128.47 (CH), 126.23 (CH), 101.24 (CH), 69.47 (CH), 69.12 (CH₂), 66.54 (CH), 62.45 (CH₂), 29.33 (CH₂), 29.17 (CH₂), 29.02 (CH₂), 28.83 (CH₂). MALDI MS 27059 m/z [M- H]⁺ (Theory: 27500 m/z [M]⁺). SEC M_w: 16150, M_n: 15870, PDI: 1.02.

Example 25 Syntheses of [Gn]-PGLSA Dendrons with Focal NHS Activated Ester

Example 25.1 Synthesis of [2-(cis-l,3-O-benzylidene glycerol)-N-succinimidyI] succinate (bzld-[Gl]-PGLSA-NHS dendron) - 2-(cώ-l,3-<9-benzylidene glycerol)succinic acid mono ester (11.47 g, 40.92 mmol), N-hydroxy succinimide (4.85 g, 42.18 mmol), and DPTS (4.26 g, 14.50 mmol), were dissolved in CH₂Cl₂ (100 mL). The reaction flask was flushed with nitrogen and then DCC (13.44 g, 65.14 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. The DCC-urea was filtered and washed with a small amount Of CH₂Cl₂ (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Following vacuum filtration, 13.0 g of a white solid was collected (84 % yield). ¹H NMR (400 MHz, CDCl₃): δ 2.76 (broad s, 4, -CH₂-CH₂-), 2.85 (m, 2, -CH₂-CH₂-), 2.96 (m, 2, -CH₂-CH₂-), 4.13 (m, 2, -CH₂-CH-CH₂-), 4.27 (m, 2, -CH₂-CH-CH₂-), 4.72 (m, 1, -CH₂-CH-CH₂-), 5.52 (s, 1, CH), 7.34 (m, 3, arom. CH), 7.47 (m, 2, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 171.32 (COOR), 169.12 (COOR), 167.82 (COOR), 137.96 (CH), 129.30 (CH), 128.51 (CH), 126.23 (CH), 101.38 (CH), 69.11 (CH₂), 66.94 (CH), 29.08 (CH₂), 26.51 (CH₂), 25.74 (CH₂). FTIR: v (cm⁴) 29318 (aliph. C-H stretch), 1820.09 and 1727 (C=O). GC-MS 378 m/z [M-H]⁺ (Theory: 377 m/z [M]⁺). Elemental Analysis C: 57.22 %; H 5.07 % (Theory: C: 57.29 %; H 5.08 %).

Example 25.2 Synthesis of bzld-[G2] -PGLSA-NHS dendron - Pd/C (10% w/w) was added to a solution of bzld- [G I]-PGLSA-NHS dendron (0.514 g, 1.36 mmol) in THF (20 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 20 min. The catalyst and activated carbon were filtered off and washed with THF (50 mL). 2-(m-l,3-Obenzylidene glycerol)succinic acid mono ester (0.975 g, 3.48 mmol) and DPTS (0.475 g, 1.61 mmol) were directly added to this solution. The reaction flask was flushed with nitrogen and then DCC (1.08 g, 5.24 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. The DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Following vacuum filtration, 0.991 g of a white solid was collected (70 % yield). ¹H NMR (400 MHz, CDCl₃): δ 2.63 (broad s, 4, -CH₂-CH₂-), 2.72 (m, 10, -CH₂-CH₂-), 2.90 (t, 2, -CH₂-CH₂-), 4.14 (m, 6, -CH₂-CH-CH₂-), 4.25 (m, 6, -CH₂-CH-CH₂-), 4.70 (m, 2, -CH₂-CH-CH₂-), 5.25 (m, 1, -CH₂-CH-CH₂-), 5.52 (s, 2, CH), 7.33 (m, 6, arom. CH), 7.47 (m, 4, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 172.31 (COOR), 171.92 (COOR), 170.35 (COOR), 169.12 (COOR), 167.80 (COOR), 138.02 (CH), 129.27 (CH), 128.49 (CH), 126.21 (CH), 101.33 (CH), 69.97 (CH₂), 69.17 (CH₂), 66.53 (CH), 62.49 (CH₂), 29.38 (CH₂), 29.05 (CH₂), 26.35 (CH₂), 25.74 (CH₂). FAB MS 814.3 m/z [M-H]⁺ (Theory: 813.8 m/z [M]⁺). Elemental Analysis C: 57.42 %; H 5.40 % (Theory: C: 57.56 %; H 5.33 %). Example 25.3 Synthesis of bzld-[G3]-PGLSA-NHS dendron - Pd/C (10% w/w) was added to a solution of bzld-[G2]-PGLSA-NHS dendron (0.687 g, 0.844 mmol) in THF (20 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 20 min. The catalyst and activated carbon were filtered off and washed with THF (50 mL). 2-(cώ-l,3-O-benzylidene glycerol)succinic acid mono ester (1.269 g, 4.53 mmol) and DPTS (0.657 g, 2.23 mmol) were directly added to this solution. The reaction flask was flushed with nitrogen and then DCC (1.08 g, 5.24 mmol) was added. The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. The DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 3:97 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. Following vacuum filtration, 0.796 g of a white solid was collected (72 % yield). ¹H NMR (400 MHz, CDCl₃): δ 2.59 (m, 9, -CH₂-CH₂-), 2.63 (m, 9, -CH₂-CHb-), 2.74 (m, 12, -CH₂-CH₂-), 2.89 (t, 2, -CH₂-CH₂-), 4.14 (m, 14, -CH₂-CH-CH₂-), 4.24 (m, 14, -CH₂-CH-CH₂-), 4.70 (m, 4, - CH₂-CH-CH₂-), 5.20 (m, 2, -CH₂-CH-CH₂-), 5.26 (m, 1, -CH₂-CH-CH₂-), 5.51 (s, 4, CH), 7.33 (m, 12, arom. CH), 7.47 (m, 8, arom. CH). ¹³C NMR (400 MHz, CDCl₃): δ 172.29 (COOR), 171.92 (COOR), 171.59 (COOR), 169.23 (COOR), 167.87 (COOR), 138.03 (CH), 129.27 (CH), 128.48 (CH), 126.21 (CH), 101.33 (CH), 69.51 (CH₂), 69.17 (CH₂), 66.54 (CH), 62.51 (CH₂), 29.37 (CH₂), 29.04 (CH₂), 28.86 (CH₂), 25.73 (CH₂). FAB MS 1686.7 m/z [M-H]⁺ (Theory: 1686.6 m/z [M]⁺). Elemental Analysis C: 57.52 %; H 5.53 % (Theory: C: 57.68 %; H 5.44 %).

Example 26

Synthesis of [G2]-PGLSA-(Z)Lys(Z) - Z-Lys(Z)-OH (1.88 g, 4.53 mmol), [G2]-PGLSA (0.401 g, 0.170 mmol), and DPTS (0.66 g, 2.24 mmol) were dissolved in THF (20 mL). The reaction flask was flushed with nitrogen and then DCC (1.43 g, 6.93 mmol) was added. Stirring at room temperature was continued for 24 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (20 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 2:98 to 4:96 methanol:CH₂Cl₂. The product was dissolved in CH₂Cl₂, filtered (to remove any DCU), and precipitated in ethyl ether at -20 ⁰C to remove remaining DCC. The ethyl ether was decanted and the precipitate was isolated to yield 1.69 g of a white solid (95.1 % yield). ¹H NMR (CDCl₃): δ 1.28 (broad s, 32, -CH₂-CH₂-CH₂- CH₂-NH-), 1.43 (broad s, 32, -CH₂-CH₂-CH₂-CH₂-NH-), 1.59 (broad s, 16, -CH₂-CH₂-CH₂- CH₂-NH-), 1.72 (broad s, 16, -CH₂-CH₂-CH₂-CH₂-NH-), 1.59 (broad s, 32, -CH₂-CH₂-CH₂- CH₂-NH-), 2.54 (broad s, 52, -CH₂-CH₂-), 4.09-4.28 (broad m, 23, -CH₂-CH-CH₂- and - CH2-CHC0-NH-), 5.00 (s, 32, -CH₂-Ph), 5.03 (s, 32, -CH₂-Ph), 5.18 (m, 14, -CH₂-CH- CH₂-), 7.25 (m, 165, arom. CH). ¹³C NMR (CDCl₃): δ 171.98 (COOR), 171.51 (COOR), 156.80 (COOR), 156.34 (COOR), 136.84 (CH), 136.44 (CH), 128.67 (CH), 128.29 (CH), 67.19 (CH), 66.76 (CH), 62.58 (CH₂), 53.96 (CH), 40.62 (CH₂), 31.80 (CH₂) 29.49 (CH₂), 28.89 (CH₂), 28.73 (CH₂), 22.56 (CH₂). MALDI MS 8708.0 m/z [M-H]⁺ (Theory: 8699.0 m/z [M]⁺). SEC M_w: 7330, M_n: 7220, PDI: 1.01.

Example 27 Synthesis of [G2]-PGLSA-Lys - [G2]-PGLSA-Z-Lys(Z) (59.0 mg, 0.00678 mmol), was dissolved in DMF (3 mL). The reaction flask was flushed with nitrogen and then 10% Pd/C (400 mg) was added and stirred vigorously. To this stirring solution, formic acid was slowly added via syringe. The solution began to bubble and give off heat. Stirring at room temperature was continued for 14 hours under nitrogen atmosphere. Upon completion, Pd/C was filtered and washed with a small amount of 1 N HCl (10 mL), which was added to the DMF solution containing the dendrimer. The resulting solution was added drip wise into a large excess of acetone. The contents were cooled to -20 ⁰C over night. The acetone was decanted and the precipitate was isolated to yield 29.0 mg of product (96.3 % yield). ¹H NMR (CDCl₃): δ 1.39 (broad m, 32, -CH₅-CH₂-CH₂-CH₂-NH-), 1.60 (broad m, 32, -CH₂- CH₂-CjH₂-CH₂-NH-), 1.83 (broad m, 16, -CH₂-CH₂-CH₂-CH₂-NH-), 1.92 (broad m, 16, - CH₂-CH₂-CH₂-CH₂-NH-), 2.53-2.60 (broad m, 52, -CH₂-CH₂-), 2.87 (broad m, 32, -CH₂- CH₂-CH₂-CH₂-NH-), 4.08 (broad m, 20, -CH₂-CH-CH₂- and -CH2-CHCO-NH-), 4.09 (broad m, 23, -CH₂-CH-CH₂- and -CH2-CHCO-NH-), 4.21 (broad m, 25, -CBb-CH-CBb- and -CH2-CHCO-NH-), 4.35 (broad m, 16, -CH₂-CH-CH₂- and -CH2-CHCO-NH-), 4.43 (broad m, 16, -CH₂-CH-CH₅- and -CH2-CHCO-NH-), 5.19 (m, 5, -CH₂-CH-CH₂-), 5.30 (m, 8, -CH₂-CH-CH₂-). ¹³C NMR (CDCl₃): δ 174.35 (COOR), 173.74 (COOR), 169.67 (COOR), 70.04 (CH), 64.21 (CH₂), 63.01 (CH₂), 52.72 (CH₂), 39.17 (CH₂), 37.07 (CH₂), 29.38 (CH₂) 28.81 (CH₂), 26.44 (CH₂), 21.78 (CH₂), 21.71 (CH₂). MALDI MS 4404 m/z [M-H]⁺ (Theory: 4407 m/z [M]⁺). SEC M_w: 7730, M_n: 7580, PDI: 1.02.

Example 28

Synthesis of [G2J-PGLSA-COOH - [G2]-PGLSA-OH (0.636 g, 0.270 mmol) was dissolved in pyridine (20 mL) and stirred while succinic anhydride (0.649 g, 6.485 mmol) was added. The reaction mixture was stirred for 16 hours at 35 oC before the pyridine was removed under reduced pressure. The contents were partially dissolved in DCM (15 mL), and 0.1 N HCl (15 mL) was then added and the mixture was stirred for an additional 15 minutes. After stirring, the organic and aqueous phases separated and a layer was formed between the two phases. While avoiding the interface, most of the aqueous and organic phases were removed. This washing procedure with 15 mL of DCM and 0.1 N HCl was repeated two more times. Any remaining organic or aqueous phase was removed first by rotoevaporation followed by lyopholization to yield 0.990 g of a highly viscous liquid (92.7 % yield). MALDI MS 3958.4 m/z [M+H]⁺, (Theory: 3957.2 m/z [M]⁺). Example 29

Synthesis of [G4]-PGLSA-COOH and [G4] -PGLSA-COO Na⁺ - [G4J-PGLSA-OH (0.140 g, 0.0131 mmol) was dissolved in pyridine (10 mL) and stirred while succinic anhydride (0.167 g, 1.68 mmol) was added. The reaction mixture was stirred for 16 hours before the pyridine was removed under reduced pressure. The contents were partially dissolved in DCM (15 mL), and 0.1 N HCl (15 mL) was then added and the mixture was stirred for an additional 15 minutes. After stirring, the organic and aqueous phases separated and a layer was formed between the two phases. While avoiding the interface, most of the aqueous and organic phases were removed. This washing procedure with 15 mL of DCM and 0.1 N HCl was repeated two more times. Any remaining organic or aqueous phase was removed first by rotoevaporation followed by lyopholization to yield 0.191 g of a highly viscous liquid (85 % yield). To dissolve the polymer in water, deionized water (10 mL) and brine (0.5 mL) were added to the solution and 0.05 N NaOH was added drop-wise to the stirring solution until the pH remained at 7.0. The dendrimer was purified via dialysis with 7,000 MW cutoff dialysis tubing for 24 hours in DI water. The water was then removed via lyopholization to obtain a white solid. ¹H NMR (D₂O): δ 2.32 (m, 130, -CH₂-CH₂-), 2.46 (m, 133, -CH₂-CH₂-), 2.58 (m, 228, -CH₂-CH₂-) 4.13-4.21 (m, 240, -CH₂-CH-CH₂-), 5.18 (m, 62, -CH₂-CH-CH₂-). ¹³C NMR (D₂O): δ 180.72 (COOH), 175.37 (COOH), 173.52 (COOR), 70.14 (CH), 69.76 (CH), 62.80 (CH₂), 34.31 (CH₂), 32.10 (CH₂), 30.72 (CH₂), 29.01 (CH₂). FTIR: v (cm^"1) 3368 (OH), 2964 (aliph. C-H stretch), 1732 (C=O), 1567 (asyra COO^" stretch), 1409 (sym COO^" stretch), 1149 (C-O stretch). MALDI MS 17168 m/z [M + Na]⁺, 8602 m/z [M + Na]²⁺, (Theory: 17120.0 m/z [M]⁺). SEC M_w: 8330, M_n: 7780, PDI: 1.11.

Example 30

Synthesis of 2-(tert-ButyldiphenylsiIanyloxy)-succinic acid 4-(2-phenyl-[l,3]dioxan-5- yl) ester - L-Malic acid (2.00 g, 15.0 mmol) was dissolved in pyridine (25 mL) and tert- butylchlorodiphenylsilane (3.9 mL, 15.0 mmol) was added via syringe. The reaction was stirred for 14 hours before the pyridine was removed by vacuum. The remaining residue was dissolved in DCM (100 mL) and washed with 0.2 N HCl (2x 100 mL). The organic layer was dried with Na₂SO₄, filtered, and evaporated. Crude 2-{tert- butyldiphenylsilanyloxy) succinic acid was subsequently dissolved in a 2:1 mixture of trifluoroacetic anhydride and THF (50 mL) respectively and heated to 50 ⁰C for 2 hours. The solvents were removed by vacuum and the crude mixture was azeotroped with toluene. The crude anhydride was dissolved in pyridine and cω-l,3-O-benzylideneglycerol (2.7 g, 54.9 mmol) was added before the solution was stirred another 14 hours. The pyridine was removed by vacuum. The remaining residue was dissolved in DCM (100 mL) and washed with 0.2 N HCl (2x 100 mL). The organic layer was dried with Na₂SO₄, filtered, and evaporated. The crude product was purified by silica gel chromatography, eluting with 79:20:1 to 59:40:1 hexane: ethyl acetate: acetic acid. 0.99 g of a viscous clear liquid were isolated following evaporation of solvents (90 % yield) evaporated to give 1.18 g of a clear viscous oil (12.3% yield). ¹H NMR (400 MHz, CDCl₃): δ 2.67 (s, 9, -CH₃), 2.78 (broad m, 2, -CH₂-CH-), 3.64 (broad m, 4, -CBb-CH-CH₂-), 4.87 (m, 1, -CH₂-CH-CH₂-) 2.78 (t, 1, - CH₂-CH-), 5.50 (s, 1, CH), 7.34 (broad m, 4, arom. CH), 7.48 (broad m, 11, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 177.54 (COOH), 175.91 (COOH), 171.63 (COOR), 138.00 (CH), 136.20 (CH), 136.14 (CH), 132.94 (CH), 130.20 (CH), 129.25 (CH), 128.41 (CH), 127.95 (CH), 127.81 (CH), 126.35 (CH), 101.41 (CH), 69.43 (CH₂), 68.78 (CH), 66.91 (CH₂), 39.92 (CH), 26.99 (CH₃), 20.95 (CH), 19.53 (CH₂). FAB-MS 535.2 m/z [M+H]⁺ (Theory: 534.67 m/z [M]⁺). Example 31

Synthesis of [GO]-PGLAA-bzld - Adipic acid (6.474 g, 44.300 mmol), cis-1,3-0- benzylideneglycerol (17.571 g, 97.508 mmol), and DPTS (10.01 g, 34.03 mmol) were dissolved in DCM (120 mL) followed by the addition of DCC (28.260 g, 136.96 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of DCM (50 mL). The crude product was purified by silica gel chromatography, eluting with 2% MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. Following vacuum filtration, 12.694 g of a white solid was collected (60.8 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.72 (s, 4, -CH₂-CH₂-CH₂-CH₂-), 2.45 (s, 4, -CH₂-CH₂-CH₂-CH₂-), 4.12 (m, 4, -CH₂-CH-CH₂-), 4.25 (m, 4, -CH₂-CH-CH₂-), 4.68 (m, 2, -CH₂-CH-CH₂-), 5.52 (s, 2, CH), 7.34 (m, 6, arom. CH), 7.48 (m, 4, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.47 (COOR), 138.01 (CH), 129.27 (CH), 128.50 (CH), 126.22 (CH), 101.43 (CH), 69.30 (CH₂), 66.08 (CH), 34.15 (CH₂), 24.49 (CH₂). FAB 471.2 m/z [M+H]⁺ (Theory: 470.51 m/z [M]⁺).

Example 32

Synthesis of [GO]-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [GO]- PGLAA-bzld (2.161 g, 4.593 mmol) in THF (30 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF solution (50 mL). The filtrate was evaporated to give 1.303 g of a clear viscous oil (96.4 % yield). ¹HNMR (400 MHz, CD₃OD): δ 1.64 (m, 4, -CH₂-CH₂- CH₂-CH₂-), 2.36 (m, 4, -CH₂-CH₂-CH₂-CBb-), 3.51 (m, 1, -CH^-CH-CH₂-), 3.64 (m, 5, - CH₂-CH-CH₂-), 3.78 (m, 1, -CH₂-CH-CH₂-), 4.03 (m, 1, -CH₂-CH-CH₂-), 4.12 (m, 1, -CH₂- CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.76 (COOR), 75.43 (CH), 69.91 (CH), 65.33 (CH₂), 62.83 (CH₂), 60.49 (CH₂), 33.52 (CH₂), 33.31 (CH₂), 24.12 (CH₂). FAB MS 295.30 m/z [M+H]⁺ (Theory: 294.30 m/z [M]⁺).

Example 33

Synthesis of adipic anhydride - Adipic acid (96.28 g, 0.6588mol) and acetic anhydride (400 mL) were combined and refluxed at 160 ⁰C for four hours. Afterwards, the acetic acid/anhydride was removed under vacuum. Next the depolymerization catalyst, zinc acetate monohydrate, was added along with a distillation apparatus and the heat was slowly increased. After 100 ⁰C, nothing was collected until 200 ⁰C when 68.79 g of a clear colorless liquid was collected (82.5 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.91 (m, 4, - CH₂-CH₂-CH₂-CH₂-), 2.67 (m, 4, -CH₂-CH₂-CH₂-CH₂-). ¹³C NMR (100.6 MHz, CDCl₃): δ 168.38 (-COOCO-), 34.60 (CH₂), 22.37 (CH₂). GC-MS 128 m/z [M]⁺ (Theory: 128.12 m/z [M]⁺).

Example 34

Synthesis of 2-(cw-l,3-0-benzylidene glycerol)adipic acid mono ester cώ-l,3-O-benzylideneglycerol (68.74 g, 0.5365 mol) was dissolved in pyridine (150 mL) followed by the addition of adipic anhydride (82.50 g, 0.4578 mol). The reaction mixture was stirred at room temperature for 18 hours before the pyridine was removed under vacuum at 35 ⁰C. The remaining solid was dissolved in DCM (400 mL) and washed two times with 0.2 N HCl (400 mL), or until the aqueous phase remained at pH 1. The organic phase was evaporated and the solid was added to deionized water (300 mL). 1 N NaOH was added until pH 7 was obtained and the product was in the aqueous solution. The aqueous phase was washed with DCM (400 mL), to extract any remaining adipic anhydride, and then readjusted to pH 4. The aqueous phase was subsequently extracted twice with DCM (400 mL), dried with Na₂SO₄, filtered, and evaporated to afford 67.53 g of a white powder (47.80 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.70 (m, 4, -CH₂-CH₂-CH₂-CH₂-), 2.35 (m, 2, - CH₂-CH₂-CH₂-CH₂-), 2.44 (m, 2, -CH₂-CH₂-CH₂-CH₂-), 4.13 (m, 2, -CH₂-CH-CH₂-), 4.25 (m, 2, -CH₂-CH-CH₂-), 4.67 (m, 1, -CH₂-CH-CH₂-), 5.53 (s, 1, CH), 7.33 (m, 3, arom. CH), 7.47 (m, 2, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 178.98 (COOH), 173.48 (COOR), 137.97 (CH), 129.30 (CH), 128.51 (CH), 126.22 (CH), 101.45 (CH), 69.28 (CH₂), 66.13 (CH), 34.13 (CH₂), 33.71 (CH₂), 24.43 (CH₂), 24.21 (CH₂). FAB MS 309.1 m/z (MH⁺) (Theory: 308.33 m/z (M⁺)).

Example 35

Synthesis of [Gl]-PGLAA-bzld - First, 2-(cis-l,3-O-benzylidene glycerol)adipic acid mono ester (7.226 g, 23.434 mmol), [GO]-PGLAA-OH (1.222 g, 4.152 mmol), and DPTS (2.830 g, 9.621 mmol) were dissolved in THF (100 mL) followed by the addition of DCC (4.32 g, 21.0 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of THF (50 mL). The crude product was purified by silica gel chromatography, eluting with 1/1 to 4/1 EtOAc:hexanes. The appropriate isolated fractions were concentrated, filtered (to remove any DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 5.99 g of a sticky solid (99.1 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.63 (m, 20, - CH₂-CH₂-CH₂-CH₂-), 2.32 (m, 12, -CH₂-CH₂-CH₂-CH₂-), 2.43 (m, 8, -CH₂-CH₂-CH₂-CHj₂- ), 4.10 (m, 12, -CH₂-CH-CH₂-), 4.25 (m, 12, -CH₂-CH-CH₂-), 4.68 (m, 4, -CH₂-CH-CH₂-), 5.21 (m, 2, -CH₂-CH-CH₂-), 5.51 (s, 4, CHj, 7.32 (m, 12, arom. CH), 7.47 (m, 8, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.40 (COOR), 172.87 (COOR), 172.55 (COOR), 138.02 (CH), 129.28 (CH), 128.49 (CH), 126.21 (CH), 101.39 (CH), 69.28 (CH₂), 66.11 (CH), 62.39 (CH₂), 34.08 (CH₂), 33.90 (CH₂), 33.75 (CH₂), 24.37 (CH₂). FAB MS 1455.6 m/z [M+H]⁺ (Theory: 1455.54 m/z [M]⁺).

Example 36 Synthesis of [Gl]-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [Gl]- PGLAA-bzld (4.870 g, 3.346 mmol) in THF (50 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF solution (50 mL). The filtrate was evaporated to give 3.669 g of a clear viscous oil (99.5 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.63 (m, 20, -CH₂- CH₂-CH₂-CH₂-), 2.36 (m, 20, -CH₂-CH₂-CH₂-CH₂-), 3.52 (m, 2, -CH₂-CH-CH₂-), 3.59-3.69 (broad m, 12, -CH₂-CH-CH₂-), 3.79 (m, 1, -CH₂-CH-CH₂-), 4.03 (m, 1, -CH^-CH-CIJ₂-), 4.14 (m, 5, -CH₂-CH-CH₂-), 4.32 (m, 4, -CH₂-CH-CH₂-), 5.24 (m, 2, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.64 (COOR), 173.36 (COOR), 172.93 (COOR), 75.42 (CH), 69.93 (CH), 69.47 (CH), 65.36 (CH₂), 62.87 (CH₂), 62.15 (CH₂), 60.50 (CH₂), 33.49 (CH₂), 33.35 (CH₂), 33.20 (CH₂), 24.11 (CH₂). MALDI-TOF MS 1125.8 m/z [M+Na]⁺ (Theory: 1103.11 m/z [M]⁺).

Example 37

Synthesis of [G2]-PGLAA-bzld - 2-(cώ-l,3-<9-benzylidene glycerol)adipic acid mono ester (10.012 g, 32.472 mmol), [Gl]-PGLAA-OH (3.397 g, 3.079 mmol), and DPTS (2.508 g, 8.527 mmol) were dissolved in THF (100 mL) followed by the addition of DCC (4.62 g, 22.4 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of THF (50 niL). The crude product was purified by silica gel chromatography, eluting with 2% MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 9.39 g of a sticky wax (89.0 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.63 (m, 52, -CH₂-CH₂-CH₂- CH₂-), 2.31 (m, 36, -CH₂-CH₂-CH₂-CH₂-), 2.41 (m, 16, -CH₂-CH₂-CH₂-CH₂-), 4.05 (m, 28, -CH₂-CH-CH₂-), 4.25 (m, 28, -CH₂-CH-CH₂-), 4.67 (m, 8, -CH₂-CH-CH₂-), 5.21 (m, 6, - CH₂-CH-CH₂-), 5.51 (s, 8, CH), 7.33 (m, 24, arom. CH), 7.46 (m, 16, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.39 (COOR), 172.87 (COOR), 172.54 (COOR), 138.02 (CH), 129.27 (CH), 128.49 (CH)₅ 126.21 (CH), 101.38 (CH), 69.27 (CH₂), 66.11 (CH), 62.39 (CH₂), 34.08 (CH₂), 33.74 (CH₂), 33.67 (CH₂), 24.37 (CH₂). MALDI MS 3449.2 m/z [M+Na]⁺ (Theory: 3425.61 m/z [M]⁺).

Example 38 Synthesis of [G2]-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [G2]- PGLAA-bzld (8.02 g, 2.34 mmol) in THF (100 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF solution (50 mL). The filtrate was evaporated to give 6.360 g of a clear viscous oil (99.4 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.62 (m, 52, -CH₂- CH₂-CH₂-CH₂-), 2.35 (m, 52, -CH₂-CH₂-CH₂-CH₂-), 3.52 (m, 5, -CH₂-CH-CH₂-), 3.59-3.71 (broad m, 25, -CH₂-CH-CH₂-), 3.79 (m, 3, -CH₂-CH-CH₂-), 4.03 (m, 3, -CH₂-CH-CH₂-), 4.14 (m, 15, -CH₂-CH-CH₂-), 4.33 (m, 12, -CH₂-CH-CH₂-), 5.25 (m, 6, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.63 (COOR), 173.27 (COOR), 172.92 (COOR), 75.42 (CH)₅ 69.94 (CH), 69.47 (CH), 65.38 (CH₂), 62.89 (CH₂), 62.17 (CH₂), 60.52 (CH₂), 33.51 (CH₂), 33.39 (CH₂), 33.22 (CH₂), 24.12 (CH₂). MALDI-TOF MS 2744.3 m/z [M+Na]⁺ (Theory: 2720.75 m/z [M]⁺).

Example 39

Synthesis of [G3]-PGLAA-bzId - 2-(cω-l,3-O-benzylidene glycerol)adipic acid mono ester (12.626 g, 40.950 mmol), [G2]-PGLAA-OH (5.263 g, 1.934 mmol), and DPTS (3.232 g, 10.989 mmol) were dissolved in THF (100 mL) followed by the addition of DCC (12.581 g, 60.975 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon reaction completion, the DCC-urea was filtered and washed with a small amount of THF (60 mL). The crude product was purified by silica gel chromatography, eluting with 1.5 to 3.0 % MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 12.22 g of a sticky wax (85.8 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.63 (broad m, 130, -CH₂-CH₂-CH₂-CH₂-), 2.31 (m, 90, -CH₂-CH₂-CH₂-CH₂-), 2.41 (m, 32, -CH₂-CH₂-CH₂- CH₂-), 4.10 (m, 62, -CH₂-CH-CH₂-), 4.24 (m, 62, -CH₂-CH-CH₂-), 4.67 (m, 16, -CH₂-CH- CH₂-), 5.19 (m, 14, -CH₂-CH-CH₂-), 5.51 (s, 16, CH), 7.32 (m, 48, arom. CH), 7.46 (m, 32, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.38 (COOR), 172.89 (COOR), 172.48 (COOR), 138.03 (CH), 129.27 (CH), 128.49 (CH), 126.21 (CH), 101.36 (CH), 69.26 (CH₂), 66.11 (CH), 62.29 (CH₂), 34.08 (CH₂), 33.83 (CH₂), 33.74 (CH₂), 33.67 (CH₂), 24.43 (CH₂), 24.36 (CH₂). MALDI-TOF MS 7390 m/z [MH-Na]⁺ (Theory: 7365.73 m/z [M]⁺).

Example 40 Synthesis of [G3J-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [G3]- PGLAA-bzld (11.03 g, 1.497 mmol) in THF (125 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF solution (75 mL). The filtrate was evaporated to give 8.69 g of a clear viscous oil (97.5 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.63 (m, 124, -CH₂-CH₂-CH₂-CH₂-), 2.35 (m, 127, -CH₂-CH₂-CH₂-CH₂-), 3.52 (m, 7, -CH₂-CH- CH₂-), 3.60-3.71 (broad m, 55, -CH₂-CH-CB₂-), 3.79 (m, 4, -CH₂-CH-CH₂-), 4.04 (m, 5, - CjH₂-CH-CH₂-), 4.14 (m, 34, -CH₂-CH-CH₂-), 4.32 (m, 29, -CH₂-CH-CH₂-), 5.25 (m, 14, - CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.82 (COOR), 173.63 (COOR), 173.36 (COOR), 173.27 (COOR), 172.92 (COOR), 75.45 (CH), 75.40 (CH), 69.96 (CH), 69.48 (CH), 65.40 (CH₂), 62.92 (CH₂), 62.23 (CH₂), 60.54 (CH₂), 33.53 (CH₂), 33.25 (CH₂), 24.15 (CH₂). MALDI-TOF MS 5975.0 m/z [M+Na]⁺ (Theory: 5956.02 m/z [M]⁺).

Example 41

Synthesis of [GO]-PGLSA-[Gl]-PGLAA-bzId - 2-(cω-l,3-(9-benzylidene glycerol)adipic acid mono ester (11.793 g, 38.248 mmol), [GO]-PGLSA-OH (1.185 g, 4.449 mmol), and

DPTS (2.853 g, 9.700 mmol) were dissolved in THF (50 mL) followed by the addition of

DCC (7.216 g, 34.973 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (50 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 1/1 to 4/1 EtOAc:hexanes. The appropriate isolated fractions were concentrated, filtered (to remove any remaining DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 7.173 g of a sticky solid (97 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.65 (m, 16, -CH₂-CH₂-CH₂-CH₂-), 2.33 (m, 8, -CH^-CH₂-CH₂- CH₂-), 2.42 (m, 8, -CH₂-CH₂-CH₂-CH₂-), 2.59 (m, 4, -CH₂-CH₂-), 4.11 (m, 12, -CH₂-CH- CH₂-), 4.24 (m, 12, -CH₂-CH-CH₂-), 4.67 (m, 4, -CH₂-CH-CH₂-), 5.20 (m, 2, -CH₂-CH- CH₂-), 5.51 (s, 4, CH), 7.33 (m, 12, arom. CH), 7.47 (m, 8, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.41 (COOR), 172.92 (COOR), 171.48 (COOR), 138.02 (CH), 129.28 (CH), 128.49 (CH), 126.21 (CH), 101.38 (CH), 69.65 (CH), 69.27 (CH₂), 66.11 (CH), 62.19 (CH₂), 34.09 (CH₂), 33.73 (CH₂), 28.97 (CH₂), 24.44 (CH₂), 24.36 (CH₂). FAB MS 1425.5 m/z [M+H]⁺ (Theory: 1427.49 m/z [M]⁺). SEC M_w: 1670, M_n: 1650, PDI: 1.01.

Example 42

Synthesis of [G0]-PGLSA-[G1]-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [GO]-PGLSA-[Gl]-PGLAA-bzld (5.900 g, 4.133 mmol) in THF (50 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (50 mL). The filtrate was evaporated to give 4.407 g of a colorless, viscous oil (99 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.63 (m, 16, -CH₂-CH₂-CH₂-CH₂-), 2.36 (m, 16, -CH₂-CH₂-CH₂-CH₂-), 2.61 (m, 4, -CH₂-CH₂-), 3.52 (m, 3, -CH₂-CH-CH₂-), 3.59-3.65 (broad m, 9, -CH₂-CH-CH₂-), 3.69 (m, 2, -CII₂-CH-CH₂-), 3.79 (m, 2, -CH₂-CH-CH₂-), 4.03 (m, 2, -CH₂-CH-CH₂-), 4.15 (m, 5, -CH₂-CH-CH₂-), 4.30 (m, 4, -CH₂-CH-CH₂-), 5.25 (m, 2, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.85 (COOR), 173.67 (COOR), 173.41 (COOR), 171.95 (COOR), 75.42 (CH), 69.93 (CH), 69.78 (CH), 65.36 (CH₂), 62.87 (CH₂), 62.04 (CH₂), 60.50 (CH₂), 33.50 (CH₂), 33.29 (CH₂), 33.19 (CH₂), 28.61 (CH₂), 24.12 (CH₂). MALDI- TOF MS 1097.5 m/z [M+Na]⁺ (Theory: 1075.06 m/z [M]⁺). SEC M_w: 1680, M_n: 1660, PDI: 1.01. Example 43

Synthesis of [G0]-PGLSA-[Gl]-PGLAA-[G2]-PGLSA-bzld - 2-(cis-l,3-O-benzylidene glycerol)succinic acid mono ester (12.758 g, 45.520 mmol), [GO]~PGLSA-[G1]-PGLAA- OH (4.284 g, 3.984 mmol), and DPTS (5.112 g, 17.381 mmol) were dissolved in THF (100 mL) followed by the addition of DCC (13.912 g, 67.436 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (50 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 2% MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any remaining DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 10.84 g of a white solid (85.7 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.60 (m, 17, -CH₂-CH₂-CH₂-CH₂-), 2.30 (m, 17, -CH₂-CH₂-CH₂-CH₂-), 2.63 (m, 20, -CH₂-CH₂-), 2.72 (m, 16, -CH₂-CH₂-), 4.11 (m, 29, - CH₂-CH-CH₂-), 4.23 (m, 29, -CH₂-CH-CH₂-), 4.70 (m, 8, -CH₂-CH-CH₂-), 5.20 (m, 6, - CH₂-CH-CH₂-), 5.51 (s, 8, CH), 7.34 (m, 12, arom. CH), 7.46 (m, 8, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.41 (COOR), 172.92 (COOR), 171.48 (COOR), 138.02 (CH), 129.28 (CH), 128.49 (CH), 126.21 (CH), 101.38 (CH), 69.65 (CH), 69.27 (CH₂), 66.11 (CH), 62.19 (CH₂), 34.09 (CH₂), 33.73 (CH₂), 28.97 (CH₂), 24.44 (CH₂), 24.36 (CH₂). MALDI-TOF MS 3172.7 m/z [M+Naf (Theory: 3173.13 m/z [M]⁺). SEC M_w: 3600, M_n: 3540, PDI: 1.02.

Example 44

Synthesis of [GO]-PGLSA-[GI]-PGLAA-[GI]-PGLSA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [G0]-PGLSA-[Gl]-PGLAA-[G2]-PGLSA-bzld (5.251 g, 1.655 mmol) in THF (100 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (50 mL). The filtrate was evaporated to give 4.011 g of a colorless, viscous oil (98.2 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.62 (m, 17, -CH₂-CH₂-CH₂-CH₂-), 2.36 (m, 17, - CH₂-CH₂-CH₂-CH₂-), 2.64 (m, 36, -CH₂-CH₂-), 3.52 (m, 2, -CH₂-CH-CH₂-), 3.60-3.66 (broad m, 26, -CH₂-CH-CH₂-), 3.69 (m, 9, -CH₂-CH-CH₂-), 3.80 (m, 1, -CH₂-CH-CH₂-), 4.18 (m, 14, -CH₂-CH-CH₂-), 4.32 (m, 12, -CH₂-CH-CH₂-), 5.25 (m, 6, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.38 (COOR), 173.05 (COOR), 172.56 (COOR), 172.24 (COOR), 172.00 (COOR), 75.81 (CH), 69.80 (CH), 69.35 (CH), 67.65 (CH₂), 65.68 (CH₂), 62.87 (CH₂), 62.42 (CH₂), 62.11 (CH₂), 60.43 (CH₂), 33.49 (CH₂), 33.20 (CH₂), 28.83 (CH₂), 28.64 (CH₂), 25.28 (CH₂), 24.09 (CH₂). MALDI-TOF MS 2492.0 m/z [M+Naf (Theory: 2468.27 m/z [M]⁺). SEC M_w: 3390, M_n: 3340, PDI: 1.02.

Example 45

Synthesis of [G0]-PGLSA-[Gl]-PGLAA-[G2]-PGLSA-[G3]-PGLAA-bzld - 2-(cw-l,3- Obenzylidene glycerol)adipic acid mono ester (10.751 g, 34.869 mmol), [GO]-PGLSA- [G1]-PGLAA-[G2]-PGLSA-OH (3.771 g, 1.528 mmol), and DPTS (1.463 g, 4.975 mmol) were dissolved in THF (120 mL) followed by the addition of DCC (10.598 g, 51.365 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (50 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 1.5% MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any remaining DCU), and directly precipitated in hexanes and cooled to -20 ⁰C overnight. The hexanes were decanted and the precipitate was isolated to yield 9.88 g of a sticky solid (90.9 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.65 (m, 81, -CH₂-Ca-CH₂-CH₂-), 2.31 (m, 52, -CH₂-CH₂-CH₂-CHb-), 2.42 (m, 32, -CH₂- CH₂-CH₂-CH₂-), 2.58 (m, 36 -CH₂-CH₂-), 4.10 (m, 62, -CH₂-CH-CH₂-), 4.23 (m, 62, -CH₂- CH-CH₂-), 4.66 (m, 16, -CH₂-CH-CH₂-), 5.19 (m, 14, -CH₂-CH-CH₂-), 5.51 (s, 16, CH), 7.33 (m, 47, arom. CH), 7.46 (m, 32, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 173.39 (COOR), 172.90 (COOR), 171.82 (COOR), 171.53 (COOR), 138.04 (CH), 129.26 (CH), 128.49 (CH), 126.22 (CH), 101.36 (CH), 69.65 (CH), 69.26 (CH₂), 66.11 (CH), 62.64 (CH₂), 62.15 (CH₂), 34.07 (CH₂), 33.73 (CH₂), 28.96 (CH₂), 28.80 (CH₂), 24.43 (CH₂), 24.35 (CH₂). MALDI-TOF MS 7137.3 m/z [M+Na]⁺ (Theory: 7113.25 m/z [M]⁺). SEC M_w: 7160, M_n: 7060, PDI: 1.01.

Example 46

Synthesis of [G0]-PGLSA-[G1]-PGLAA-[G2]-PGLSA-[G3]-PGLAA-OH - Pd(OH)₂/C (10% w/w) was added to a solution of [GO]-PGLSA-[G1]-PGLAA-[G2]-PGLSA-[G3]- PGLAA-bzld (9.175 g, 1.290 mmol) in THF (100 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (50 mL). The filtrate was evaporated to give 7.218 g of a colorless, viscous oil (98.1 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.63 (m, 83, -CH₂-CH₂-CH₂-CH₂-), 2.37 (m, 83, -CH₂-CH₂-CH₂-CH₂-), 2.61 (m, 36, -CH₂-CH₂-), 3.52 (m, 8, -CH₂-CH-CH₂-), 3.60-3.71 (broad m, 57, -CH₂-CH-CH₂-), 3.80 (m, 4, -CH₂-CH- CH₂-), 4.03 (m, 5, -CH₂-CH-CH₂-), 4.11-4.23 (m, 34, -CH₂-CH-CH₂-), 4.30 (m, 29, -CH₂- CH-CH₂-), 5.25 (m, 14, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.85 (COOR), 173.67 (COOR), 173.41 (COOR), 171.95 (COOR), 75.42 (CH), 69.93 (CH), 69.78 (CH), 65.36 (CH₂), 62.87 (CH₂), 62.04 (CH₂), 60.50 (CH₂), 33.50 (CH₂), 33.29 (CH₂), 33.19 (CH₂), 28.61 (CH₂), 24.12 (CH₂). MALDI-TOF MS 5730.3 m/z [M+Naf (Theory: 5703.54 m/z [M]⁺). SEC M_w: 6570, M_n: 6490, PDI: 1.01.

Example 47

Synthesis of [GO]-PGLSA-[G1]-PGLAA-[G2]-PGLSA-[G3]-PGLAA-[G4]-PGLSA- bzld - 2-(cώ-l,3-O-benzylidene glycerol)succinic acid mono ester (11.572 g, 41.286 mmol), [GO]-PGLSA-[GI]-PGLAA-^]-PGLSA-[GS]-PGLAA-OH (5.593 g, 0.981 mmol), and DPTS (4.094 g, 13.919 mmol) were dissolved in THF (80 mL) followed by the addition of DCC (12.596 g, 61.048 mmol). The reaction was stirred at room temperature for 14 hours under nitrogen atmosphere. Upon completion, the DCC-urea was filtered and washed with a small amount of THF (50 mL) and the solvent was evaporated. The crude product was purified by silica gel chromatography, eluting with 1.5% to 5.0% MeOH in DCM. The appropriate isolated fractions were concentrated, filtered (to remove any remaining DCU), and directly precipitated in hexanes and cooled to -20 ⁰C over 48 hours. The hexanes were decanted and the precipitate was isolated to yield 11.50 g of a white solid (83.2 % yield). ¹H NMR (400 MHz, CDCl₃): δ 1.59 (m, 83, -CH₂-CH₂-CH₂-CH₂-), 2.30 (m, 83, -CH₂-CH₂- CH₂-CH₂-), 2.62 (m, 104, -CH₂-CH₂-), 2.70 (m, 63, -CH₂-CH₂-), 4.12 (m, 130, -CH₂-CH- CH₂-), 4.22 (m, 130, -CH₂-CH-CH₂-), 4.68 (m, 32, -CH₂-CH-CH₂-), 5.18 (m, 30, -CH₂-CH- CH₂-), 5.50 (s, 32, CH), 7.33 (m, 97, arom. CH), 7.46 (m, 66, arom. CH). ¹³C NMR (100.6 MHz, CDCl₃): δ 172.88 (COOR), 172.53 (COOR), 172.25 (COOR), 171.89 (COOR), 138.04 (CH), 129.26 (CH), 128.48 (CH), 126.22 (CH), 101.28 (CH), 69.14 (CH₂), 66.54 (CH), 62.60 (CH₂), 33.81 (CH₂), 33.66 (CH₂), 29.35 (CH₂), 29.03 (CH₂), 24.30 (CH₂). SEC M_w: 10440, M_n: 10290, PDI: 1.02. Example 48

Synthesis of [G0]-PGLSA-[G1]-PGLAA-[G2]-PGLSA-[G3]-PGLAA-[G4]-PGLSA-OH

- Pd(OH)₂/C (10% w/w) was added to a solution of [GO]-PGLSA-[G1]-PGLAA-[G2]- PGLSA-[G3]-PGLAA-[G4]-PGLSA-bzld (2.084 g, 0.1478 mmol) in THF (80 mL). The flask for catalytic hydrogenolysis was evacuated and filled with 60 psi OfH₂ before shaking for 10 hours. The catalyst was filtered and washed with THF (75 niL). The filtrate was evaporated to give 1.652 g of a colorless, viscous oil (99.1 % yield). ¹H NMR (400 MHz, CD₃OD): δ 1.62 (m, 80, -CH₂-CH₂-CH₂-CH₂-), 2.37 (m, 80, -CH₂-CH₂-CH₂-CH₂-), 2.64 (m, 164, -CH₂-CH₂-), 3.52 (m, 12, -CH₂-CH-CH₂-), 3.63-3.71 (broad m, 160, -CH₂-CH- CH₂-), 3.80 (m, 6, -CH₂-CH-CH₂-), 4.06 (m, 14, -CH₂-CH-CH₂-), 4.20 (m, 62, -CH₂-CH- CH₂-), 4.30 (m, 60, -CH₂-CH-CH₂-), 5.25 (m, 30, -CH₂-CH-CH₂-). ¹³C NMR (100.6 MHz, CD₃OD): δ 173.40 (COOR), 173.06 (COOR), 172.58 (COOR), 75.82 (CH), 69.90 (CH), 69.34 (CH), 67.64 (CH₂), 62.45 (CH₂), 62.15 (CH₂), 60.46 (CH₂), 33.25 (CH₂), 28.87 (CH₂), 28.67 (CH₂), 25.27 (CH₂), 24.12 (CH₂). MALDI-TOF MS 11299.1 m/z [M+Naf (Theory: 11276.39 m/z [M]⁺). SEC M_w: 9150, M_n: 9000, PDI: 1.02.

Example 49

Synthesis of PEG-([G0]-PGLSA-bzId)₂ - This example is shown for PEG of 3400 Mw, but we have also used PEG of 10,000 and 20,000 Mw. PEG, M_n=3400, (10.0 g, 2.94 mmol), which was dried under vacuum at 120 ⁰C for three hours, and [2-(cis- 1,3-0- benzylidene glyceroty-N-succinimidyl] succinate (4.03 g, 10.7 mmol) were dissolved in CH₂Cl₂ (100 mL) and stirred under nitrogen. TEA (2.0 mL, 14 mmol) was added by syringe and stirring was continued for 14 hours. Any remaining activated ester was quenched by the addition of fresh TEA (1.0 mL, 7.2 mmol) and n-propanol (1.0 mL, 11 mmol), which was allowed to stir for another 10 hours. After removing most of the solvent, the product was precipitated in cold ethyl ether (700 mL) and collected to yield 11.1 g of a white solid (97 % yield). ¹H NMR obtained. Elemental Analysis C: 55.31 %; H 8.58 % (Theory C: 55.56 %; H 8.66 %). MALDI MS M_w: 4020, M_n: 3940, PDI: 1.02. SEC M_w: 3980, M_n: 3950, PDI: 1.03.

Example 50

Synthesis of PEG-([G0]-PGLSA-OH)₂ - Pd/C (10 % w/w) was added to a solution of PEG-([G0]-PGLSA-bzld)₂ (5.07 g, 1.29 mmol) in 80 mL of 9:1 ethyl acetate/methanol. The apparatus for catalytic hydrogenolysis was evacuated and filled with 50 psi of H₂ before shaking for 8 hours. The catalyst was filtered off and washed with ethyl acetate (20 mL). The filtrate was evaporated and the remaining white solid was redissolved in a minimal amount Of CH₂Cl₂ (15 mL)and precipitated in cold ethyl ether (600 mL) to give 4.52 g of a white solid (93 % yield). ¹H NMR obtained. Elemental Analysis C: 53.49 %; H 8.78 % (Theory C: 53.69 %; H 8.85 %). MALDI MS M_w: 3780, M_n: 3730, PDI: 1.01. SEC M_w: 3860, M_n: 3710, PDI: 1.021.

Example 51 Synthesis of PEG-([Gl]-PGLSA-bzld)₂ - PEG-([G0]-PGLSA-OH)₂ (5.81 g, 1.55 mmol), which was dried under vacuum at 80 ⁰C for three hours, and [2-(cw-l,3-<9-benzylidene glycero^-N-succinimidyl] succinate (4.35 g, 11.5 mmol) were dissolved in CH₂Cl₂ (70 niL) and stirred under nitrogen. TEA (1.75 mL, 13.0 mmol) was added by syringe and stirring was continued for 14 hours. Any remaining activated ester was quenched by the addition of fresh TEA (1.0 mL, 7.2 mmol) and n-propanol (1.0 mL, 11 mmol), which was allowed to stir for another 10 hours. After removing most of the solvent, the product was precipitated in cold ethyl ether (700 mL) and collected to yield 7.15 g (96 % yield). ¹H NMR obtained. MALDI MS M_w: 4520, M_n: 4480, PDI: 1.01. SEC M_w: 4420, M_n: 4240, PDI: 1.04.

Example 52 Synthesis of PEG-([G1]-PGLSA-OH)₂ - Pd/C (10 % w/w) was added to a solution of

PEG-([Gl]-PGLSA-bzld)₂ (5.53 g, 1.15 mmol) in 80 mL of 9:1 ethyl acetate/methanol. The apparatus for catalytic hydrogenolysis was evacuated and filled with 50 psi of H₂ before shaking for 8 hours. The catalyst was filtered off and washed with ethyl acetate (20 mL).

The filtrate was evaporated and the remaining white solid was redissolved in a minimal amount OfCH₂Cl₂ (15 mL) and precipitated in cold ethyl ether (700 mL) to give 4.71 g of a white solid (92 % yield). ¹H NMR obtained. MALDI MS M_w: 4320, M_n: 4280, PDI: 1.01.

SEC M_w: 4390, M_n: 4230, PDI: 1.04.

Example 53

Synthesis of PEG-([G1]-PGLSA-MA)₂ - PEG-([G1]-PGLSA-OH)₂ (1.03 g, 0.232 mmol), which was dried under vacuum at 80 ⁰C for three hours, was dissolved in CH₂Cl₂ (40 mL) and stirred under nitrogen before the addition of methacryloyl chloride (1.93 g, 5.12 mmol).

TEA (0.80 mL, 5.74 mmol) was added by syringe and stirring was continued for 14 hours.

The mixture was diluted with more CH₂Cl₂ (60 mL) and washed twice with 0.1 N HCl (100 mL). After drying with Na₂SO₄, filtering, and removing most of the solvent, the product was precipitated in cold ethyl ether and collected to yield 1.08 g (94 % yield). ¹H NMR obtained. SEC M_w: 4610, M_n: 4420, PDI: 1.04. Example 54

Synthesis of PEG-([G2]-PGLSA-bzld)₂ - PEG-([G1]-PGLSA-OH)₂ (0.697 g, 0.150 mmol), which was dried under vacuum at 80 ⁰C for three hours, and [2-(cw-l,3-O- benzylidene glyceroty-N-succinimidyl] succinate (1.01 g, 2.68 mmol) were dissolved in CH₂Cl₂ (30 niL) and stirred under nitrogen. TEA (0.50 mL, 3.59 mmol) was added by syringe and stirring was continued for 14 hours. Any remaining activated ester was quenched by the addition of fresh TEA (1.0 mL, 7.2 mmol) and n-propanol (1.0 mL, 11 mmol), which was allowed to stir for another 10 hours. After removing most of the solvent, the product was precipitated in cold ethyl ether (400 mL) and collected to yield 0.940 g (93 % yield). ¹H NMR obtained.

Example SS

Synthesis of ([GI]-PGLSA-MA)₂-PEG - ([G1]-PGLSA-OH)₂-PEG (0.500 g, 0.113 mmol) was dissolved in DCM (15 mL) and stirred under nitrogen before methacrylic anhydride (0.56 mL, 3.76 mmol) was added by syringe. DMAP (86.0 mg, 0.704 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of methanol (0.1 mL, 3.95 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (35 mL) and washed with 0.1 N HCl (50 mL) and brine (50 mL). The organic phase was dried with Na₂SO₄ and filtered before the PEG-based dendrimer was precipitated in cold (-20 ⁰C) ethyl ether (300 mL) and collected to yield 0.519 g of a white solid (93 % yield). ¹R NMR (CDCl₃): δ 1.90 (m, 19, -CH₃), 2.61 (m, 21, -CH₂-CH₂-), 3.42 (t, 2, -CH₂-CH₂-), 3.55-3.65 (broad m, 285, -CH₂-CH₂-), 3.77 (t, 2, -CH₂- CH₂-), 4.09-4.37 (broad m, 29, -CH₂-CH-CH₂-), 5.22 (m, 2, -CH₂-CH-CH₂-), 5.35 (m, 2, - CH₂-CH-CH₂-), 5.57 (m, 6, CH), 6.07 (m, 6, CH). ¹³C NMR (CDCl₃): δ 171.89 (COOR), 135.84 (CH), 126.64 (CH), 70.75 (CH₂), 69.45 (CH), 62.61 (CH₂), 28.87 (CH₂), 18.43 (CH₃). FTIR: v (cm^"1) 2873 (aliph. C-H stretch), 1736 (C=O). MALDI MS M_w: 5012, M_n: 4897, PDI: 1.02. SEC M_w: 3910, M_n: 3740, PDI: 1.04. T_m = 40.8.

Example 56

Synthesis of ([G2]-PGLSA-bzld)₂-PEG - ([G1]-PGLSA-OH)₂-PEG (3.25 g, 0.737 mmol), and 2-(cώ-l,3-O-benzylidene glycerol) succinic acid mono ester anhydride (12.68 g, 23.37 mmol) were dissolved in DCM (50 mL) and stirred under nitrogen. DMAP (0.588 g, 4.81 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of n-propanol (2.5 mL, 28 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (50 mL) and washed with 0.1 N HCl (100 mL), saturated sodium bicarbonate (100 mL 3x), and brine (100 mL). The organic phase was dried with Na₂SO₄, Filtered, and concentrated before the PEG-based dendrimer was precipitated in cold (-20 ⁰C) ethyl ether (400 mL) and collected to yield 4.57 g of a white solid (91 % yield). ¹H NMR (CDCl₃): δ 2.61 (broad m, 40, -CH₂-CH₂-), 2.72 (broad m, 16, -CH₂-CH₂-), 3.43 (t, 2, -CH₂-CH₂-), 3.55-3.65 (broad m, 280, -CH₂-CH₂-), 3.77 (t, 2, -CH₂-CH₂-), 4.13 (broad m, 28, -CH₂-CH-CH₂-), 4.22 (broad m, 28, -CH₂-CH-CH₂-), 4.69 (m, 8, -CH₂-CH-CH₂-), 5.20 (m, 6, -CH₂-CH-CH₂-), 5.50 (s, 8, CH), 7.32 (m, 24, arom. CH), 7.46 (m, 16, arom. CH). ¹³C NMR (CDCl₃): δ 172.28 (COOR), 171.91 (COOR), 171.57 (COOR), 138.01 (CH), 129.26 (CH), 128.48 (CH), 126.21 (CH), 101.33 (CH), 70.56 (CH₂), 69.50 (CH), 69.16 (CH₂), 66.53 (CH), 64.08 (CH₂), 29.49 (CH₂), 29.21 (CH₂). FTIR: v (cm⁴) 2879(aliph. C-H stretch), 1736 (C=O). MALDI MS M_w: 6642, M_n: 6492, PDI: 1.02. SEC M_w: 4860, M_n: 4680, PDI: 1.04. T_m = 31.4.

Example 57 Synthesis of ([G2]-PGLSA-OH)₂-PEG - Pd(OH)₂/C (10 % w/w) was added to a solution of ([G2]-PGLSA-bzld)₂-PEG (3.26 g, 0.500 mmol) in 25 mL of 2:1 DCM/methanol. The apparatus for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 8 hours. The catalyst was filtered off and washed with DCM (20 mL). The PEG-based dendrimer was isolated after evaporation of solvents to give 2.86 g of a white solid (98 % yield). ¹H NMR (CDCl₃): δ 2.63 (broad m, 56, -CH₂-CH₂-), 3.42 (s, 4, -CH₂- CH₂-), 3.50-3.67 (broad m, 285, -CH₂-CH₂-), 3.72 (broad m, 27, -CH₂-CH-CH₂-), 4.14-4.29 (broad m, 32, -CH₂-CH-CKb-), 4.88 (m, 8, -CH₂-CH-CH₂-), 5.22 (m, 6, -CH₂-CH-CH₂-). ¹³C NMR (CDCl₃): δ 172.56 (COOR), 172.32 (COOR), 76.01 (CH), 70.78 (CH₂), 69.56 (CH), 69.22 (CH₂), 64.14 (CH₂), 63.52 (CH₂), 62.60 (CH₂), 61.93 (CH₂), 29.44 (CH₂), 29.21 (CH₂), 28.98 (CH₂). FTIR: v (cm^"1) 3452 (OH), 288. (aliph. C-H stretch), 1735 (C=O). MALDI MS M_w: 5910, M_n: 5788, PDI: 1.02. SEC M_w: 5340, M_n: 5210, PDI: 1.03. T_1n = 36.5.

Example 58

Synthesis of ([G2]-PGLSA-MA)₂-PEG - ([G2]-PGLSA-OH)₂-PEG (0.501 g, 0.0863 mmol) was dissolved in DCM (15 mL) and stirred under nitrogen before methacrylic anhydride (0.50 mL, 3.36 mmol) was added by syringe. DMAP (72.1 mg, 0.990 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of methanol (0.1 niL, 3.95 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (35 mL) and washed with 0.1 N HCl (50 mL) and brine (50 mL). The organic phase was dried with Na₂SO₄ and filtered before the PEG- based dendrimer was precipitated in cold (-20 ⁰C) ethyl ether (300 mL) and collected to yield 0.534 g of a white solid (90 % yield). ¹H NMR (CDCl₃): δ 1.89 (m, 47, -CH₃), 2.60 (m, 65, -CH₂-CH₂-), 3.56-3.67 (broad m, 387, -CH₂-CH₂-), 3.77 (t, 2, -CH₂-CH₂-), 4.12-4.37 (broad m, 81, -CH₂-CH-CH₂-), 5.21 (m, 13, -CH₂-CH-CH₂-), 5.33 (m, 7, -CH₂-CH-CH₂-), 5.56 (m, 16, CH), 6.06 (m, 16, CH). ¹³C NMR (CDCl₃): δ 171.89 (COOR), 135.84 (CH), 126.64 (CH), 70.75 (CH₂), 69.45 (CH), 62.61 (CH₂), 28.87 (CH₂), 18.43 (CH₃). FTIR: v (cm⁴) 2873 (aliph. C-H stretch), 1736 (C=O). %). MALDI MS M_w: 6956, M_n: 6792, PDI: 1.02. SEC M_w: 4580, M_n: 4390, PDI: 1.04. T_m = 27.0.

Example 59

Synthesis of ([G3]-PGLSA-bzld)₂-PEG - ([G2]-PGLSA-OH)₂-PEG (2.13 g, 0.367 mmol), and 2-(cw-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (12.71 g, 23.43 mmol) were dissolved in DCM (45 mL) and stirred under nitrogen. DMAP (0.608 g, 4.98 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of n-propanol (2.0 mL, 22 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (55 mL) and washed with 0.1 N HCl (100 mL), saturated sodium bicarbonate (100 mL 3x), and brine (100 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the PEG-based dendrimer was precipitated in cold (-20 ⁰C) ethyl ether (400 mL) overnight and collected to yield 3.35 g of a white solid (92 % yield). ¹H NMR (CDCl₃): δ 2.61 (broad m, 84, -C]H₂-CH₂-), 2.74 (broad m, 36, -CH₂-CH₂-), 3.43 (t, 2, -CH₂-CH₂-), 3.56-3.65 (broad m, 278, -CH₂-CH₂-), 3.78 (t, 2, -CH₂-CH₂-), 4.13 (broad m, 60, -CH₂-CH-CH₂-), 4.21 (broad m, 60, -CH₂-CH- CH₂-), 4.69 (m, 16, -CH₂-CH-CH₂-), 5.19 (m, 14, -CH₂-CH-CH₂-), 5.50 (s, 16, CH), 7.32 (m, 46, arom. CH), 7.46 (m, 30, arom. CH). ¹³C NMR (CDCl₃): δ 172.28 (COOR), 171.91 (COOR), 138.03 (CH), 129.26 (CH), 128.48 (CH), 126.21 (CH), 101.31 (CH), 70.76 (CH₂), 69.49 (CH), 69.16 (CH₂), 66.53 (CH), 62.47 (CH₂), 29.35 (CH₂), 29.02 (CH₂), 28.83 (CH₂). FTIR: v (cm⁴) 2868 (aliph. C-H stretch), 1735 (C=O). MALDI MS M_w: 10215, M_n: 9985, PDI: 1.02. SEC M_w: 7020, M_n: 6900, PDI: 1.02. T_g = -13.6. Example 60

Synthesis of ([G3]-PGLSA-OH)₂-PEG - Pd(OH)₂/C (10 % w/w) was added to a solution of ([G3]-PGLSA-bzld)₂-PEG (2.88 g, 0.288 mmol) in 30 mL of 2:1 DCM/methanol. The apparatus for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 8 hours. The catalyst was filtered off and washed with DCM (20 mL). The PEG-based dendrimer was isolated after evaporation of solvents to give 2.86 g of a white solid (98 % yield). ¹H NMR ((CD₃)₂CO):δ 2.64 (broad m, 120, -CH₂-CH₂-), 3.49-3.60 (broad m, 286, -CH₂-CH₂-), 3.64-3.75 (broad m, 33, -CH₂-CH-CH₂-), 4.00-4.12 (broad m, 42, -CH₂-CH-CH₂-), 4.13-4.29 (broad m, 68, -CH₂-CH-CH₂-), 4.64 (t, 2, -CH₂-CH-CH₂-), 4.85 (t, 2, -CH₂-CH-CH₂-), 5.26 (m, 14, -CH₂-CH-CH₂-). ¹³C NMR ((CD₃)₂CO): δ 171.85 (COOR), 171.64 (COOR), 76.09 (CH), 73.70 (CH₂), 70.56 (CH), 69.52 (CH₂), 66.19 (CH), 63.87 (CH₂), 62.31 (CH₂), 61.65 (CH₂), 60.69 (CH₂). FTIR: v (cm⁴) 3432 (OH), 2925 (aliph. C-H stretch), 1734 (C=O). MALDI MS M_w: 8765, M_n: 8575, PDI: 1.02. SEC M_w: 8090, M_n: 7820, PDI: 1.03. T_g = -38.2.

Example 61

Synthesis of ([G3]-PGLSA-MA)₂-PEG - ([G3]-PGLSA-OH)₂-PEG (0.223 g, 0.0260 mmol) was dissolved in THF (15 mL) and stirred under nitrogen before methacrylic anhydride (1.10 mL, 7.38 mmol) was added by syringe. DMAP (90.0 mg, 0.737 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of methanol (0.2 mL, 7.89 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (35 mL) and washed with 0.1 N HCl (50 mL) and brine (50 mL). The organic phase was dried with Na₂SO₄ and filtered before the PEG- based dendrimer was precipitated in cold (-20 ⁰C) ethyl ether (300 mL) and collected to yield 0.248 g of a white solid (89 % yield). ¹B NMR (CDCl₃): δ 1.90 (m, 76, -CH₃), 2.62 (m, 111, -CH₂-CH₂-), 3.56-3.67 (broad m, 285, -CjH₂-CH₂-), 4.14-4.38 (broad m, 114, -CH₂- CH-CH₂-), 5.23 (m, 13, -CH₂-CH-CH₂-), 5.35 (m, 10, -CH₂-CH-CH₂-), 5.56 (m, 25, CH), 6.07 (m, 25, CH). ¹³C NMR (CDCl₃): δ 171.87 (COOR), 135.91 (CH), 126.71 (CH), 70.76 (CH₂), 69.47 (CH), 62.62 (CH₂), 28.88 (CH₂), 18.43 (CH₃). FTIR: v (cm-¹) 2874 (aliph. C- H stretch), 1734 (C=O). MALDI MS M_w: 10722, M_n: 10498, PDI: 1.02. SEC M_w: 7000, M_n: 6820, PDI: 1.03. T_g = -37.9. Example 62

Synthesis of ([G4]-PGLSA-bzld)₂-PEG - ([G3]-PGLSA-OH)₂-PEG (1.82 g, 0.212 mmol), and 2-(cM-l,3-O-benzylidene glycerol)succinic acid mono ester anhydride (15.93 g, 29.36 mmol) were dissolved in THF (50 rnL) and stirred under nitrogen. DMAP (0.537 g, 4.40 mmol) was added and stirring was continued for 14 hours. Any remaining anhydride was quenched by the addition of n-propanol (2.5 mL, 28 mmol), which was allowed to stir for another 5 hours. The reaction was diluted with DCM (50 mL) and washed with 0.1 N HCl (100 mL), saturated sodium bicarbonate (100 mL 3x), and brine (100 mL). The organic phase was dried with Na₂SO₄, filtered, and concentrated before the PEG-based dendrimer was precipitated in ethyl ether (400 mL) and collected to yield 3.11 g of a white solid (87 % yield). ¹H NMR (CDCl₃): δ 2.61 (broad m, 180, -CH₂-CH₂-), 2.70 (broad m, 64, -CH₂-CH₂- ), 3.43 (t, 2, -CH₂-CH₂-), 3.56-3.65 (broad m, 286, -CH₂-CH₂-), 3.78 (t, 2, -CH₂-CH₂-), 4.11 (broad m, 125, -CHb-CH-CH₂-), 4.23 (broad m, 125, -CH₂-CH-CH₂-), 4.68 (m, 32, -CH₂- CH-CH₂-), 5.20 (m, 30, -CH₂-CH-CH₂-), 5.49 (s, 32, CH), 7.32 (m, 93, arom. CH), 7.46 (m, 62, arom. CH). ¹³C NMR (CDCl₃): δ 172.28 (COOR), 171.90 (COOR), 171.60 (COOR), 138.04 (CH), 129.26 (CH), 128.48 (CH), 126.21 (CH), 101.29 (CH), 70.76 (CH₂), 69.46 (CH), 69.15 (CH₂), 66.53 (CH), 62.57 (CH₂), 29.34 (CH₂), 29.18 (CH₂), 29.02 (CH₂), 28.83 (CH₂). FTIR: v (cm⁴) 2865 (aliph. C-H stretch), 1734 (C=O). MALDI MS M_w: 17289, M_n: 16968, PDI: 1.02. SEC M_w: 8110, M_n: 7950, PDI: 1.02. T_g = 5.3.

Example 63

Synthesis of ([G4]-PGLSA-OH)₂-PEG - Pd(OH)₂/C (10 % w/w) was added to a solution of ([G4]-PGLSA-bzld)₂-PEG (2.88 g, 0.170 mmol) in 30 mL of 2:1 DCM/methanol. The apparatus for catalytic hydrogenolysis was evacuated and filled with 60 psi of H₂ before shaking for 8 hours. The catalyst was filtered off and washed with DCM (20 mL). The PEG-based dendrimer was isolated after evaporation of solvents to give 2.86 g of a white solid (98 % yield). ¹H NMR ((CD₃)₂CO): δ 2.64 (broad m, 248, -CH₂-CH₂-), 3.49-3.60 (broad m, 296, -CH₂-CH₂-), 3.66 (broad m, 50, -CH₂-CH-CH₂-), 3.82 (broad m, 42, -CH₂- CH-CH₂-), 4.04-4.16 (broad m, 66, -CH₂-CH-CH₂-), 4.28 (broad m, 124, -CH₂-CH-CH₂-), 4.86 (m, 10, -CH₂-CH-CH₂-), 5.27 (m, 30, -CH₂-CH-CH₂-). ¹³C NMR ((CDs)₂CO): δ 172.20 (COOR), 70.45 (CH₂), 70.10 (CH)₅ 69.92 (CH₂), 65.96 (CH), 62.31 (CH₂). FTIR: v (cm^"1) 3445 (OH), 2931 (aliph. C-H stretch), 1713 (C=O). MALDI MS M_w: 14402, M_n: 14146, PDI: 1.02. SEC M_w: 9130, M_n: 8980, PDI: 1.02. T_g = -18.0. Example 64

Synthesis of bzld- [G1]-PGLSA-TBDPS

4.00 g (0.014 mol) of bzld-[Gl]-PGLSA-CO₂H and 3.24 g (0.048 mol) of imidazole were stirred in 15 niL of DMF. Next, 6.4 niL (0.024 mol) of diphenyl-t-butyl silyl chloride were added and the reaction was stirred at 25 ⁰C for 48 hours. The DMF was removed, the product was dissolved in CH₂Cl₂, washed with sat. NaHCO₃ and water, dried over Na₂SO₄, filtered, rotovapped, and dried on the vacuum line. The product was purified by column chromatography (4:1 hexanes:EtOAc) affording 6.38 g of product as a viscous opaque oil (86% yield). R_f = 0.13 in 4:1 hexanes:EtOAc. ¹H NMR (CDCl₃): δ 1.09 (s, 9H, t-butyl), 2.78-2.84 (m, 4H, -CH₂-CH₂), 4.11-4.15 (m, 2Η, -CH₂-CH-CH₂-), 4.23-4.26 (m, 2Η, -CH₂- CH-CH₂-), 4.70-4.71 (m, 1Η, -CH₂-CH-CH₂-), 5.54 (s, IH, CH), 7.33-7.42, 7.48-7.50, 7.67- 7.68 (m, 15Η, arom. bzld and phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.34 (-C-(CHs)₃), 27.07 (-C-(CH₃)₃), 29.72, 30.96 (succ. -CH₂-), 66.46, 69.18 (glycerol, 2C, -CH₂-), 101.39 (O-CH-O), 126.23, 127.94, 128.50, 129.28, 130.29, 131.93, 135.51 (arom. CH), 137.99 (arom. bzld -C-), 171.53, 172.52 (succ. -C(=O)-) ppm. GC-MS: 519.2 m/z (MH⁺) (theory: 518.2 m/z (M⁺)). HR-FAB: 517.2028 m/z (M-H⁺) (theory: 518.2125 m/z (M⁺)). Elemental analysis: C, 69.18%; H, 6.69% (theory: C, 69.47%; H, 6.61%).

Example 65 Synthesis Of HO-[Gl]-PGLSA-TBDPS

2.41 g (4.65 mmol) of bzld-[Gl]-PGLSA-TBDPS was dissolved in 45 mL of THF, and 1.0 g of 20% Pd(OH)₂/C was added. The solution was then placed in a Parr tube on a hydrogenator, evacuated, flushed with hydrogen, and shaken under 50 psi H₂ for 3 hours. The solution was then filtered over wet celite. The product was purified by column chromatography (1:1 Hex:EtOAc increasing to 1 :4 Hex:EtOAc) to yield 1.9 g of a clear oil (95% yield). ¹H NMR (CDCl₃): δ 1.08 (s, 9H, t-butyl), 2.02 (b s, 2H₅ -OH), 2.64-2.85 (m, 4Η, -CH₂-CH₂), 3.70-3.72, 4.07-4.14 (m, 4Η, -CH₂-CH-CH₂-), 4.83-4.86 (m, 1Η, -CH₂-CH- CH₂-), 7.33-7.44, 7.62-7.65 (m, 1OH, arom. phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.30 (-C-(CΗ₃)₃), 27.03 (-C-(CH₃)s), 29.77, 31.37 (succ. -CH₂-), 62.45 (glycerol, -CH₂-), 75.86 (CH₂-CH-CH₂), 127.97, 130.36, 132.67, 135.49 (phenyl CH), 172.65, 178.24 (succ. - C(=O)-) ppm. FAB-MS: 431 m/z (M-H⁺) (theory: 430.57 m/z (M⁺)). Acetyl derivative of compound HO-[G1]-PGLSA-TBDPS: Compound HO-[G1]-PGLSA-TBDPS was a hydroscopic oil and repeated attempts to obtain satisfactory EA failed. Thus, we decided to prepare the acetyl analog for elemental analysis. 0.44 g (1.02 mmol) of HO-[G1]-PGLSA-TBDPS was stirred in 30 mL Of CH₂Cl₂ with 0.30 g (1.02 mmol) of DPTS, 0.15 mL (2.66 mmol) of freshly distilled acetic acid, and 0.63 g (3.07 mmol) of DCC. The solution was stirred at RT for 18 hours. The DCU precipitate was filtered and the solution was evaporated. A solution of 1:1 ethyl acetate :hexanes was added and impurities precipitated. The solution was filtered, concentrated and further purified by column chromatography (3:1 hexanes:EtOAc), to afford 0.44 g of product (83% yield). R_f = 0.19 (4:1 hexanes:EtOAc) ¹H NMR (CDCl₃): δ 1.08 (s, 9H, t-butyl), 1.87-1.93 (m, 6H, -CH₃), 2.50-2.71 (m, 4Η, -CH₂-CH₂), 3.96-4.19 (m, 4Η, -CH₂-CH-CH₂-), 5.06-5.18 (m, 1Η, -CH₂-CH-CH₂-), 7.22-7.33, 7.51-7.56 (m, 1OH, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.10 (-C-(CΗ₃)₃), 20.61 (OC-CH₃), 26.82 (-C-(CH₃)₃), 29.14, 30.62 (succ. - CH₂-), 62.12, 69.28 (glycerol, -CH₂-), 127.71, 130.09, 131.65, 135.27 (arom. CH), 170.52, 171.19, 171.58 ( -C(=O)-) ppm. FAB-MS: 515.4 m/z (MH⁺) (theory: 514.6 m/z (M⁺)). Elemental analysis: C, 62.76%; H, 6.69% (theory: C, 63.01%; H, 6.66%). SEC: M_w = 547, M_n = 528, PDI = 1.04.

Example 66

Synthesis of bzld-[G2]-PGLSA-TBDPS 1.90 g (4.41 mmol) of HO-[G1]-PGLSA-TBDPS was stirred in 100 mL Of CH₂Cl₂ with 1.30 g (1 equiv; 4.41 mmol) of DPTS, 2.72 g (9.70 mmol; 2.2 equiv) of 2(cis-l,3-<9-benzylidene glycerol)succinic acid monoester, and 2.00 g (9.70 mmol; 2.2 equiv) of DCC. The solution was stirred at RT for 18 hours. The DCU precipitate was filtered off and the solution was evaporated. A solution of 1:1 ethyl acetate :hexanes was added and impurities precipitated. The solution was filtered, concentrated and further purified by column chromatography (1:1 hexanes:EtOAc) to afford 3.70 g of product (88% yield). R_f = 0.216 (1:1 hexanes:EtOAc). ¹H NMR (CDCl₃): δ 1.08 (s, 9H, t-butyl), 2.57-2.79 (m, 12H, -CH₂-CH₂), 4.08-4.14, 4.16- 4.22 (m, 12Η, -CH₂-CH-CH₂-), 4.70-4.71 (m, 2Η, -CH₂-CH-CH₂-), 5.21 (m, IH, CH), 5.49- 5.54 (m, 1Η, CH), 7.32-7.41, 7.47-7.49, 7.64-7.58 (m, 20Η, arom. bzld and phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.31 (-C-(CΗ₃)₃), 27.04 (-C-(CH₃)₃), 28.98, 29.33, 30.81 (succ. -CH₂-), 62.48, 66.50, 69.16, 69.43 (glycerol, -CH₂-), 101.33 (0-CH-O), 126.22, 127.95, 128.49, 129.26, 130.32, 131.92, 135.49 (arom. CH), 138.02 (arom. bzld -C-), 171.93, 172.28 (succ. -C(=O)-) ppm. GC-MS: 955.3 m/z (MH⁺) (theory: 954.4 m/z (M⁺)). Elemental analysis: C, 64.35%; H, 6.29% (theory: C, 64.14%; H, 6.12%). SEC: M_w = 940, M_n = 930, PDI = 1.01.

Example 67 Synthesis of bzld-[G2]-PGLSA-acid

1.00 g (1.04 mmol) of of bzld-[G2]-PGLSA-TBDPS was dissolved in 75 mL of THF. Next, 1.25 g (3.96 mmol) of tetrabutylammonium fluoride trihydrate was added to the solution and it was stirred at RT for 1 hour. After one hour the reaction was complete as indicated by TLC. The solution was diluted with 25 mL OfH₂O and acidified with IN HCl to a pH of 3. The product was extracted into CH₂Cl₂, dried over Na₂SO₄, concentrated and dried on the vacuum line. The product was purified by column chromatography (0-5% MeOH in CH₂Cl₂; R_f = 0.24) for 0.65 g of product (87% yield). ¹H NMR (CDCl₃): δ 2.55- 2.77 (m, 12H, -CH₂-CH₂), 4.10-4.17, 4.24-4.31 (m, 12Η, -CH₂-CH-CH₂-), 4.74-4.75 (m, 2Η, -CH₂-CH-CH₂-), 5.28-5.31 (m, IH, CH), 5.52-5.54 (m, 2Η, CH), 7.33-7.38, 7.47-7.49 (m, 10Η, arom. bzld CH) ppm. ¹³C NMR (CDCl₃): δ 28.72, 29.03, 29.38 (succ. -CH₂-), 62.68, 66.56, 69.16 (glycerol, -CH₂-), 101.44 (O-CH-O), 126.23, 128.50, 129.33 (arom. CH), 137.75 (arom. bzld -C-), 172.67, 175.16 (succ. -C(=O)-) ppm. GC-MS: 715.2 m/z (M-H) (theory: 716.2 m/z (M⁺)). Elemental analysis: C, 58.71%; H, 5.82% (theory: C, 58.66%; H, 5.63%). SEC: M_w = 810, M_n = 800, PDI = 1.01.

Example 68

Synthesis of HO-[G2]-PGLSA-TBDPS

1.55 g (1.62 mmol) of of bzld-[G2]-PGLSA-TBDPS was dissolved in 40 mL of THF and 1.0 g of 20% Pd(OH)₂/C was added. The solution was then placed in a Parr tube on a hydrogenator and shaken under 50 psi H₂ for 4 hours. The solution was then filtered over wet celite, rotoevaporated, and purified by column chromatography (0-25% acetone in EtOAc) to yield 1.12 g of product (95% yield). R_f = 0.25 (1:3 acetone :EtO Ac). ¹H NMR (CDCl₃): δ 1.07 (s, 9H, t-butyl), 2.25 (b s, 4H, -OH), 2.58-2.82 (m, 12Η, -CH₂-CH₂), 3.71- 3.74, 4.09-4.26 (m, 12Η, -CH₂-CH-CH₂-), 4.87-4.99, 5.24-5.25 (m, 3Η, -CH₂-CH-CH₂-), 7.34-7.43, 7.63-7.48 (m, 1OH, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 14.52 (-C-(CHs)₃), 25.78 (-C-(CH₃)S), 26.99, 29.30, 30.51, 30.81 (succ. -CH₂-), 62.08, 63.44, 68.17, 70.23 (glycerol, -CH₂-), 125.71, 127.96, 130.35, 135.45 (phenyl), 171.94, 172.40 (succ. -C(=O)-) ppm. GC-MS: 779.5 m/z (MH⁺) (theory: 778.3 m/z (M⁺)). SEC: M_w = 800, M_n = 792, PDI

=1.01

Acetyl derivative of HO-[G2]-PGLSA-TBDPS:

Compound HO-[G2]-PGLSA-TBDPS was a hydroscopic oil and repeated attempts to obtain satisfactory EA failed. Thus, we decided to prepare the acetyl analog for elemental analysis. 0.55 g (0.70 mmol) of of HO-[G2]-PGLSA-TBDPS was stirred in 40 mL Of CH₂Cl₂ with 0.39 g (1.34 mmol) of DPTS, 0.19 mL (3.36 mmol) of freshly distilled acetic acid, and 0.87 g (4.20 mmol) of DCC. The solution was stirred at RT for 18 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in a minimum of CH₂Cl₂, cooled to 10 ⁰C and filtered. The resulting solution was concentrated and further purified by column chromatography (0-5% acetone in CH₂Cl₂) to afford 0.49g of product (66% yield). R_f = 0.17 (5% acetone in CH₂Cl₂) ¹H NMR (CDCl₃): δ 1.07 (s, 9H, t-butyl), 2.04 (s, 12H, -CH₃), 2.55-2.83 (m, 12Η, -CH₂-CH₂), 4.09-4.32 (m, 12Η, -CH₂-CH-CH₂-), 5.20-5.29 (m, 3Η, -CH₂-CH-CH₂-), 7.32-7.44, 7.61-7.67 (m, 1OH, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.10 (-C-(CΗ₃)₃), 20.67 (OC-CH₃), 26.82 (-C-(CH₃)₃), 28.60, 28.80, 29.10, 30.59 (succ. -CH₂-), 62.11, 62.31, 69.39 (glycerol, -CH₂-), 127.72, 130.09, 131.67, 135.27 (arom. CH), 170.50, 171.33, 171.61 ( -C(=O)-) ppm. FAB-MS: 947.9 m/z (MH⁺) (theory: 947.0 m/z (M⁺)). Elemental analysis: C, 57.15%; H, 6.26% (theory: C, 57.07%; H, 6.17%). SEC: M_w = 1075, M_n = 1041, PDI = 1.03.

Example 69

Synthesis of bzld-[G3]-PGLSA-TBDPS

The bzld-[G3]-PGLSA-TBDPS dendron was synthesized by two methods, first by coupling of a bzld-[G2]-PGLSA-acid dendron to a HO-[G1]-PGLSA-TBDPS dendron convergently, and second by coupling compound to a HO-[G2]-PGLSA-TBDPS dendron (7) divergently.

Convergently: 1.05 g (1.47 mmol) of bzld-[G2]-PGLSA-acid was stirred in 75mL of CH₂Cl₂, and 0.29 g (0.67 mmol) Of HO-[Gl]-PGLSA-TBDPS, 0.20 g (0.67 mmol) DPTS, and 0.41 g (2.00 mmol) DCC were added. The solution was stirred at RT for 48 hours. The DCU precipitate was filtered off and the solution was evaporated. The product was purified by column chromatography (3:7 hexanes: EtOAc, R_f = 0.08) with a yield of 0.99 g (82% yield). Divergently: 0.55 g (0.71 mmol) of a HO-[G2]-PGLSA-TBDPS was stirred in 50 mL of CH₂Cl₂, and 0.42 g (1.41 mmol) of DPTS, 0.871 g (3.11 mmol) of 2(cis-l,3-O-Benzylidene Glycerol)Succinic Acid Monoester, and 0.64 g (3.12 mmol) of DCC were added. The solution was stirred under nitrogen at RT for 18 hours. The DCU precipitate was filtered and the solution was evaporated. The product was purified by column chromatography (3:7 hexanes:EtOAc) to afford 0.71 g of product (54% yield). R_f = 0.08 (3:7 hexanes:EtOAc). ¹H NMR (CDCl₃): δ 1.08 (s, 9H, t-butyl), 2.54-2.92 (m, 28H, -CH₂-CH₂), 4.08-4.15, 4.22- 4.27 (m, 28Η, -CH₂-CH-CH₂-), 4.71 (s, 4Η, -CH₂-CH-CH₂-), 5.21-5.24 (m, 3H, CH), 5.52 (s, 4Η, CH), 7.31-7.42, 7.42-7.49, 7.65-7.67 (m, 30Η, arom. bzld and phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.31 (-C-(CHs)₃), 27.04 (-C-(CH₃)S), 29.35, 30.81 (succ. -CH₂-), 62.49, 66.53, 69.16, 69.47 (glycerol, -CH₂-), 101.33 (0-CH-O), 126.21, 127.94, 128.48, 129.26, 130.32, 135.47 (arom. CH), 138.02 (arom. bzld -C-), 171.90, 172.28 (succ. -C(O)-) ppm. GC-MS: 1825.6 m/z (M-H⁺) (theory: 1827.9 m/z (M⁺)). HR-FAB: 1825.6124 m/z (M-H⁺) (theory: 1826.6233 m/z (M⁺)). Elemental analysis: C, 60.66%; H, 5.85% (theory: C, 61.11%; H, 5.85%). SEC: M_w = 1830, M_n = 1810, PDI = 1.01.

Example 70

Synthesis of bzld-[G3]-PGLSA-acid

2.00 g (1.09 mmol) of bzld-[G3]-PGLSA-TBDPS was dissolved in 125 mL of THF. Next, 1.3 g (4.1 mmol) of tetrabutylammonium fluoride trihydrate was added to the solution. The mixture was stirred at RT for 1 hour. After one hour the reaction was complete as indicated by TLC. The solution was diluted with 25 mL of H₂O and acidified with IN HCl to a pH of

3. The product was extracted into CH₂Cl₂, dried over Na₂SO₄, rotoevaporated and dried on the vacuum line. The product was purified by column chromatography (0-5% MeOH in CH₂Cl₂) to afford 1.44 g of product (83% yield). R_f = 0.21 (5% MeOH in CH₂Cl₂). ¹H

NMR (CDCl₃): δ 2.58-2.75 (m, 28H, -CH₂-CH₂), 4.11-4.16, 4.19-4.27 (m, 28Η, -CH₂-CH-

CH₂-), 4.71-4.72 (m, 4Η, -CH₂-CH-CH₂-), 5.21-5.28 (m, 3H, CH), 5.52-5.53 (m, 4Η, CH),

7.32-7.37, 7.46-7.49 (m, 20Η, arom. bzld CH) ppm. ¹³C NMR (CDCl₃): δ 29.05, 29.36

(succ. -CH₂-), 62.51, 66.58, 69.16 (glycerol, -CH₂-), 101.36 (0-CH-O), 126.21, 128.49, 129.29 (arom. CH), 137.95 (arom. bzld -C-), 171.83, 173.01 (succ. -C(O)-) ppm. GC-

MS: 1587.5 m/z (M-H⁺) (theory: 1588.5 m/z (M⁺)). Elemental analysis: C, 58.02%; H,

5.60% (theory: C, 58.18%; H, 5.58%). SEC: M_w = 1650, M_n = 1620, PDI = 1.02. Example 71

Synthesis of HO-[G3]-PGLSA-TBDPS

0.53 g (0.29 mmol) of bzld-[G3]-PGLSA-TBDPS was dissolved in 50 mL of THF in a Parr tube. 0.4 g of 20% Pd(OH)₂/C was added and the flask was evacuated and filled with 50 psi of H₂. The mixture was shaken for 8 hours, then filtered over wet celite. The filtrate was dried to produce a clear oil which was purified by column chromatography (0-50% acetone in EtOAc) to afford 0.38 g of product (88% yield). R_f = 0.23 (1:1 acetone:EtOAc). ¹H NMR (CDCl₃): δ 1.3 (s, 9H, t-butyl), 2.52-2.86 (m, 28H, -CH₂-CH₂), 3.44-3.94 (m, 24, -CH₂-CH- CH₂- and -OH), 4.10-4.38, (m, 12Η, -CH₂-CH-CH₂-), 4.82-4.92 (m, 4Η, CH), 5.18-5.30 (m, 3Η, CH), 7.28-7.43, 7.50-7.54, 7.60-7.66 (m, 10Η, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 19.04 (-C-(CΗ₃)₃), 24.44 (-C-(CHs)₃), 26.76, 27.12, 28.82, 28.97, 29.10, 30.57 (succ. -CH₂- ), 61.17, 62.33, 63.21, 69.30, 75.52 (glycerol, -CH₂-), 127.72, 130.11, 131.57, 134.36, 135.20 (arom. CH), 171.66, 171.72, 171.99, 172.27, 172.38, 172.46 (succ. -C(O)-) ppm. MALDI-MS: 1475.56 m/z (MH⁺) (theory: 1475.5 m/z (M⁺)). SEC: M_w = 2101, M_n = 1994, PDI = 1.05.

Acetyl derivative of compound of HO-[G3]-PGLSA-TBDPS:

Compound HO-[G3]-PGLSA-TBDPS was a hydroscopic oil and repeated attempts to obtain satisfactory EA failed. Thus, we decided to prepare the acetyl analog for elemental analysis. 0.24 g (0.16 mmol) of HO-[G3]-PGLSA-TBDPS was stirred in 40 mL Of CH₂Cl₂ with 0.19 g (0.65 mmol) of DPTS, 0.09 mL (1.55 mmol) of freshly distilled acetic acid, and 0.40 g (1.94 mmol) of DCC. The solution was stirred at RT for 18 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in a minimum Of CH₂Cl₂, cooled to 10 ⁰C and filtered. The resulting solution was concentrated and further purified by column chromatography (8:2 hexanes:EtOAc to 3:7 hexanes:EtOAc) to afford 0.18 g of product (63% yield). R_f = 0.15 (3:7 hexanes:EtOAc) ¹H NMR (CDCl₃): δ 1.10 (s, 9H, t-butyl), 1.99 (s, 24H, -CH₃), 2.48-2.78 (m, 28Η, -CH₂-CH₂), 4.02-4.30 (m, 28Η, - CH₂-CH-CH₂-), 5.12-5.26 (m, 7Η, -CH₂-CH-CH₂-), 7.25-7.38, 7.55-7.61 (m, 1OH, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 18.87 (-C-(CHs)₃), 20.46 (OC-CH₃), 26.61 (-C-(CHs)₃), 26.95, 28.47, 28.55, 28.64, 28.90, 30.39 (succ. -CH₂-), 61.90, 62.10, 69.02, 69.22 (glycerol, -CH₂-), 127.52, 129.90, 131.48, 135.05 (arom. CH), 170.26, 171.14, 171.40, 171.46 ( - C(O)-) ppm. FAB-MS: 1812.2 m/z (MH⁺) (theory: 1811.8 m/z (M⁺)). Elemental analysis: C, 53.95%; H, 6.12% (theory: C, 53.70%; H, 5.90%). SEC: M_w = 1943, M_n = 1882, PDI = 1.03. Example 72

Synthesis of bzld-[G4]-PGLSA-TBDPS

The bzld-[G4]-PGLSA-TBDPS dendron was synthesized by two methods, first by coupling of bzld-[G2]-PGLSA-acid dendron to a HO- [G2] -PGLS A-TBDPS dendron convergently, and secondly by coupling the monoester 2(cis-l,3-O-Benzylidene Glycerol)Succinic Acid Monoester to a HO-[G3]-PGLSA-TBDPS dendron divergently. Convergently: 0.14 g (0.18 mmol) of HO-[G2]-PGLSA-TBDPS was dissolved in 30 mL of CH₂Cl₂. Next, 0.05 g (0.18 mmol) of DPTS, 0.82 g (1.10 mmol) of bzld-[G2]-PGLSA-acid and 0.22 g (1.10 mmol) of DCC were added. The solution was stirred at RT under nitrogen for 72 hours. The DCU was filtered, the filtrate was concentrated to dryness and the residue was resuspended in a minimum of cold THF. The solution was filtered, concentrated and purified by column chromatography (1:1 hexanes:EtOAc to 1:4 hexanes:EtOAc, R_f = 0.14) to afford 0.48 g of product (75% yield). Divergently: 0.38 g (0.26 mmol) of HO-[G3]-PGLSA-TBDPS was dissolved in 50 mL of CH₂Cl₂. Next, 1.00 g (3.57 mmol) of 2(cis-l,3-O-Benzylidene Glycerol) Succinic Acid Monoester, 0.10 g (0.34 mmol) of DPTS, and 0.656 g (3.57 mmol) of DCC were added to the mixture. The solution was stirred for 48 hours under nitrogen at RT. The DCU precipitate was filtered, concentrated and purified by column chromatography (1:1 hexanes:EtOAc to 1 :4 hexanes:EtOAc, R_f = 0.14) to afford 0.572 g of product (60% yield). ¹H NMR (CDCl₃): δ 1.07 (s, 9H, t-butyl), 2.55-2.77 (m, 6OH, -CH₂-CH₂), 4.07-4.15, 4.22- 4.25 (m, 60Η, -CH₂-CH-CH₂-), 4.70 (s, 8Η, -CH₂-CH-CH₂-), 5.19-5.21 (m, 7H, CH), 5.51 (s, 8Η, CH), 7.30-7.40, 7.46-7.48, 7.63-7.65 (m, 50Η, arom. bzld and phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 14.40 (-C-(CΗ₃)₃), 27.03 (-C-(CHs)₃), 29.02, 29.35 (succ. -CH₂-), 62.47, 66.53, 69.16, 69.49 (glycerol, -CH₂-), 101.31 (OCH-O), 126.21, 127.94, 128.48, 129.26, 135.47 (arom. CH), 138.03 (arom. bzld -C-), 171.50, 171.90, 172.27 (succ. -C(=O)-) ppm. MALDI-MS: 3574.54 m/z (MH⁺) (theory: 3573.54 m/z (M⁺)). Elemental analysis: C, 59.49%; H, 5.70% (theory: C, 59.19%; H, 5.74%). SEC: M_w = 3420, M_n = 3350, PDI = 1.02. Example 73

Synthesis of [G3]-PGLSA-bzld Dendrimer

0.019 g (0.084 mraol) of [GO]-PGLSA-OH, 12 was dissolved in 50 niL Of CH₂Cl₂. Next, 0.64 g (0.40 mmol) of compound bzld-[G3]-PGLSA-acid, 0.074 g (0.25 mmol) of DPTS, and 0.10 g of DCC (0.50 mmol) were added. The solution was stirred for 72 hours at RT under nitrogen. The DCU was filtered off and the filtrate was concentrated. The additional DCU was precipitated in cold THF and filtered. The product was purified by column chromatography (0-5% MeOH in CH₂Cl₂) to yield 0.40 g of product (73% yield). ¹H NMR (CDCl₃): δ 2.60-2.74 (m, 116H, -CH₂-CH₂), 4.08-4.17 (m, 60Η, -CH₂-CH-CH₂-), 4.22-4.26 (m, 60Η, -CH₂-CH-CH₂-), 4.70 (s, 16Η, -CH₂-CH-CH₂-), 5.20-5.23 (m, 14H, CH), 5.51 (s, 16Η, CH), 7.32-7.36, 7.46-7.48 (m, 80H₅ arom. bzld CH) ppm. ¹³C NMR (CDCl₃): δ 29.02, 29.35 (succ. -CH₂-), 62.47, 66.54, 69.16 (glycerol, -CH₂-), 101.31 (0-CH-O), 126.21, 128.48, 129.26 (arom. CH), 138.01 (arom. bzld -C-), 171.83, 172.29 (succ. -C(=O)-) ppm. MALDI: 6553.4 m/z (MH⁺) (theory: 6552.2 m/z (M⁺). Elemental analysis: C, 58.50%; H, 5.48% (theory: C, 58.29%; H, 5.57%). SEC: M_w = 4740, Mn = 4590, PDI = LOl.

Example 74

Synthesis of [G3]-PGLSA-OH Dendrimer, 14 0.33 g (0.051 mmol) of [G3]-PGLSA-bzld was dissolved in 50 mL of a 9:1 solution of THF and MeOH in a Parr tube. Next, 0.50 g of 20% Pd(OH)2/C was added and the flask was evacuated and filled with 50 psi of H2. The mixture was shaken for 7 hours, then filtered over wet celite. The filtrate was dried to produce 0.25 g of a clear oil (0.049 mmol, 97% yield). ¹H NMR (CD₃OD): δ 2.64 (m, 116, -CH2-CH2-), 3.51 (m, 26, -CH2-CH-CH2- ), 3.67 (m, 28, -CH2-CH-CH2-), 3.80 (m, 12, -CH2-CH-CH2-), 4.05 (m, 14, -CH2-CH- CH2-), 4.14 (m, 14, -CH2-CH-CH2-), 4.22 (m, 22, -CH2-CH-CH2-), 4.30 (m, 22, -CH2- CH-CH2-), 5.26 (m, 14, -CH2-CH-CH2) ppm. ¹³C NMR (CD₃OD): δ. 28.61 (CH2), 62.41 (CH2), 62.87 (CH2), 65.67 (CH₂), 67.64 (CH), 69.91 (CH), 172.86 (COOR) ppm. MALDI- MS: 5144.8 m/z (MH⁺) (theory: 5142.5 m/z (M⁺)). Elemental analysis: C, 48.07%; H, 5.84% (theory: C, 48.11%; H₅ 5.84%). SEC M_w: 5440; M_n: 5370; PDI: 1.01.

Example 75

Synthesis of [G3] -PGLSA-MA Dendrimer (50% derivatized) 6 023723

0.22 g (0.041 mmol) of [G3]-PGLSA-OH was dissolved in 5 mL of DMF. Next, 0.20 g (1.66 mmol) of DMAP was then added followed by 0.10 mL (0.67 mmol, 0.5 eq. to the peripheral hydroxyl groups on [G3]-PGLSA-OH) of freshly distilled niethacrylic anhydride. After 4.5 hours the reaction was complete as indicated by TLC. 0.03 mL (0.67 mmol) of MeOH was added to the reaction and allowed to stir for an additional 20 minutes. The solution was precipitated into 300 mL of cold ethyl ether. The ether was decanted off and the remaining oily reside was diluted with 20 mL of CH₂Cl₂. The organic phase was washed with 1 N HCl and brine. The organic phase was dried over Na₂SO₄, filtered, and concentrated to approximately 2 mL. This concentrated solution was precipitated in 300 mL of cold ethyl ether. The ether was decanted off and the resulting oily residue was dried under reduced pressure to yield 0.20 g of product (78% yield). ¹H NMR (CDCl₃): δ 1.90 (s, 42H, -CH₃), 2.55-2.77 (m, 116Η, -CH₂-CH₂), 3.61-3.78 (m, 30Η, -CH₂-CH-CH₂-), 4.07- 4.30 (m, 120H, -CH₂-CH-CH₂-), 5.58-5.62 (m, 16Η, =CH), 6.03-6.16 (m, 16Η, =CH) ppm. ¹³C NMR (CDCl₃): δ 18.24 (-CH₃), 29.56, 29.75 (succ. -CH₂-), 61.52, 62.09, 62.14, 65.17, 65.83, 69.39, 69.56, 70.04, 73.23, 75.89 (glycerol -CH₂-), 171.04, 171.25, 171.37, 171.58, 171.79, 172.14, 172.51 ppm. MALDI-MS: 6224.6 m/z (MH⁺) (theory: 6231.6 m/z (M⁺)). SEC: M_w = 3525, M_n = 2708, PDI = 1.30.

Example 76 Synthesis of bzld-[G3] -PGLSA-PEG-OMe

0.29 g (0.18 mmol) of bzld-[G3]-PGLSA-acid was dissolved in 75 mL Of CH₂Cl₂. Next 0.45 g (0.09 mmol) of 5000 MW polyethylene glycol) mono-methyl ether (PEG-OMe; MALDI-MS: M_w = 5147, M_n = 5074, PDI = 1.01), 0.037 g (0.18 mmol) of DCC, and 0.026 g (0.09 mmol) of DPTS were added to the solution. The solution was stirred under nitrogen at RT for 168 hours. The DCU was filtered and the filtrate was concentrated to dryness. The resulting residue was resuspended in THF, cooled, and the DCU was filtered. The resulting solution was precipitated in ethyl ether. The solid was dissolved in THF, stirred with Amberlyst A-21 ion-exchange resin (Aldrich) (weakly basic resin) to eliminate the excess 9. The solution was filtered and the filtrate was dried over Na₂SO₄, dissolved in CH₂Cl₂, washed with 0.1 N HCl, and dried over Na₂SO₄ to yield 0.53 g of a solid white product (89% yield). ¹H NMR (CDCl₃): δ 2.60-2.73 (m, 28H, -CH₂-CH₂), 3.36 (s, MME CH₃) 3.57-3.64 (m, 406Η, PEG CH₂), 4.11-4.26 (m, 28Η, -CH₂-CH-CH₂-), 4.71 (m, 4Η, - CH₂-CH-CH₂-), 5.21-5.23 (m, 3H, CH), 5.52-5.54 (m, 4H, CH), 7.32-7.37, 7.46-7.49 (m, 2OH, arom. bzld CH) ppm. ¹³C NMR (CDCl₃): δ 29.36, 29.90 (succ. -CH₂-), 62.48, 66.53, 69.17 (glycerol, -CH₂-), 70.77 (PEG, -CH₂-), 101.33 (O-CH-O), 126.21, 128.48, 129.26 (arom. CH), 137.80 (arom. bzld -C-), 171.90 (succ. -C(⁸O)-) ppm. MALDI-MS: M_w = 6671, M_n = 6628 PDI = 1.01 (theoretical MW = 6588). SEC: M_w = 6990, M_n = 6670, PDI = 1.04.

Example 77

Synthesis of HO-[G3]-PGLSA-PEG-OMe

0.52 g of bzld-[G3]-PGLSA-PEG-OMe was dissolved in 40 mL of THF. Next, 0.10 g of 20% Pd(OH)₂/C was added. The reaction vessel was evacuated and flushed with hydrogen.

The solution was shaken for 3 hours under 50 psi H₂ at RT. The Pd(OH)₂/C was removed by filtering over wet celite. The filtrate was dried and precipitated in ethyl ether to yield

0.40 g of an opaque hydroscopic solid (83% yield). ¹H NMR (CDCl₃): δ 2.60-2.70 (m,

28H, -CH₂-CH₂), 3.36 (s, MME CH₃) 3.53-3.78 (b m, 422Η, PEG CH₂ and -CH₂-CH-CH₂-), 4.17-4.27 (m, 12Η, -CH₂-CH-CH₂-), 4.92 (m, 4Η, -CH₂-CH-CH₂-), 5.21-5.23 (m, 3H, CH) ppm. ¹³C NMR (DMSO): δ 29.14, 29.36 (succ. -CH₂-), 60.25 (-CH₃ OMe), 63.22, 66.54,

69.87 (glycerol, -CH₂-), 70.43 (PEG, -CH₂-), 172.35, 172.57 (succ. -C(O)-) ppm.

MALDI-MS: M_w = 6302, M_n = 6260, PDI = 1.01 (theoretical MW = 6136). SEC: M_w =

6660, M_n = 6460, PDI = 1.03.

Example 78

Synthesis of MA-[G3]-PGLSA-PEG-OMe

0.39 g (0.064 mmol) of HO-[G3]-PGLSA-PEG-OMe was dissolved in 30 mL of CH₂Cl₂. Next, 10 mg (0.08 mmol) of DMAP and 0.15 mL methacrylic anhydride (1.0 mmol) were added and the solution was stirred at RT under nitrogen overnight. The solution was then washed with 0.1 N HCl, dried over Na₂SO₄, condensed, and precipitated in ether to afford 0.41 g of product (96% yield). ¹H NMR (CDCl₃): δ 1.92 (s, 24 H, -CH₃- methacrylate), 2.63 (m, 28H, -CH₂-CH₂), 3.36 (s, MME CH₃) 3.59-3.67 (m, 406Η, PEG CH₂), 4.19-4.39 (m, 28Η, -CH₂-CH-CH₂-), 5.24 (m, 4Η, -CH₂-CH-CH₂), 5.35 (m, 3H, CH), 5.59 (s, 8Η, - CH₂- methacrylate), 6.10 (s, 8Η, -CH₂- methacrylate) ppm. MALDI-MS: M_w = 7080, M_n = 7008, PDI = 1.01 (theoretical MW = 6780). SEC: M_w = 6918, M_n = 6465, PDI = 1.07. Example 79

Synthesis ofMyr-[G2]-PGLSA-TBDPS

0.45 g (0.58 mmol) of compound OH-[G2]-PGLSA-TBDPS was dissolved in 75 mL of CH₂Cl₂ with 0.63 g (2.77 mmol) of myristic acid(Myr), 0.34 g (1.16 mmol) of DPTS₅ and 0.72 g (3.47 mmol) of DCC. The reaction was stirred at RT for 16 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in 50 mL of ethanol, cooled to 0 ⁰C for 6 hours and filtered. The precipitate was resuspended in 75 mL of CH₂Cl₂, washed with 75 mL of H₂O, dried over Na₂SO₄, and the solvent evaporated to yield 0.84 g of product (89% yield). ¹H NMR (CDCl₃): δ 0.80-0.89 (t, 12H, - CH₃), 1.08 (s, 9Η, t-butyl), 1.14-1.34 (m, 8OH, myristic -CH₂-), 1.50-1.64 (m, 8Η, C(=O)- CH₂-CH₂-CH₂-), 2.22-2.33 (t, 8H, C(=O)-CH₂-CH₂-), 2.53-2.83 (m, 12H, succinic -CH₂- CH₂), 4.08-4.34 (m, 12Η, -CH₂-CH-CH₂-), 5.18-5.30 (m, 3Η, -CH₂-CH-CH₂-), 7.32-7.44, 7.61-7.67 (m, 1OH, phenyl CH) ppm. ¹³C NMR (CDCl₃): δ 14.25, 22.67, 24.81 , 26.85, 28.81, 28.79, 29.12, 29.24, 29.36, 29.53, 29.64, 31.97, 34.05, 61.88, 62.34, 69.17, 127.66, 130.13, 135.28, 138.77, 171.34, 171.69, 173.32 ppm. FAB-MS: 1620.1 m/z (MH⁺) (theory: 1620.29 m/z (M⁺)). Elemental analysis: C, 68.84%; H, 9.69% (theory: C, 68.94%; H, 9.58%). SEC: M_w = 2168, M_n = 2135, PDI = 1.02.

Example 80 Synthesis of Myr-[G2]-PGLSA-acid

0.81 g (0.50 mmol) of Myr-[G2]-PGLSA-TBPDS was dissolved in 100 mL of THF. Next, 0.55 g (1.75 mmol) of tetrabutylammonium fluoride trihydrate was added to the solution. The mixture was stirred at RT for 1 hour. After one hour the reaction was complete as indicated by TLC. The solution was diluted with 25 mL of H₂O and acidified with IN HCl to a pH of 3. The product was extracted into EtOAc, dried over Na₂SO₄, rotoevaporated and dried on the vacuum line. The product was purified by column chromatography (0-3% MeOH in CH₂Cl₂) to afford 0.60 g of product (87% yield). R_f = 0.23 (3% MeOH in CH₂Cl₂). ¹H NMR (CDCl₃): δ 0.82-0.88 (t, 12H, -CH₃), 1.20-1.31 (m, 80Η, myristic -CH₂-), 1.53-1.64 (m, 8Η, -C(=O)-CH₂-CH₂-CH₂-), 2.26-2.33 (t, 8H, -C(=O)- CH₂-CH₂-), 2.60-2.68 (m, 12H, -CH₂-CH₂-), 4.11-4.34 (m, 12Η, -CH₂-CH-CH₂-), 5.19-5.35 (m, 3Η, -CH₂-CH-CH₂-) ppm. ¹³C NMR (CDCl₃): δ 14.16, 22.78, 24.98, 28.56, 28.87, 29.07, 29.24, 29.47, 29.63, 29.87, 32.01, 34.04, 62.02, 62.64, 69.16, 69.93, 171.47, 171.68, 173.51 ppm. FAB-MS: 1382.9 m/z (M-H⁺) (theory: 1381.9 m/z (M⁺)). Elemental analysis: C, 66.72%; H, 9.91% (theory: C, 66.92%; H, 9.92%). SEC: M_w = 2074, M_n = 2040, PDI = 1.02.

Example 81 Synthesis of 2-benzyl-l,3.-di(Myr-[G2]-PGLSA)₂-glyceroI

0.85 g (0.62 mmol) of compound Myr-[G2]-PGLSA-acid was dissolved in 75 mL of CH₂Cl₂ with 0.05 g (0.26 mmol) of 2-benzyl-glycerol, 0.08 g (0.26 mmol) of DPTS, and 0.16 g (0.77 mmol) of DCC. The reaction was stirred at RT for 16 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in 50 mL of ethanol, cooled to 0 ⁰C for 6 hours and Filtered. The precipitate was purified by column chromatography (20-50% EtOAc in hexanes) to yield 0.63 g of product (85% yield). R_f = 0.17 (30% EtOAc in hexanes). ¹H NMR (CDCl₃): δ 0.81-0.88 (t, 24H, -CH₃), 1.17- 1.34 (m, 160Η, myristic -CH₂-), 1.52-1.63 (m, 16Η, C(=O)-CH₂~CH₂-CH₂-), 2.24-2.32 (t, 16H, C(O)-CH₂-CH₂-), 2.58-2.66 (m, 24H, succinic -CH₂-CH₂), 3.77-3.85 (m, 1Η, -CH₂- CH-CH₂-), 4.04-4.38 (m, 28H, -CH₂-CH-CH₂-), 4.59-4.65 (s, 2Η, benzyl -CH₂-), 5.17- 5.34 (m, 6Η, -CH₂-CH-CH₂-), 7.25-7.34 (m, 5H, aromatic CH) ppm. MALDI-MS: 2933.4 m/z (M+Na⁺) (theory: 2933.0 m/z (M+Na⁴)). Elemental analysis: C, 67.92%; Η, 9.79% (theory: C, 67.69%; Η, 9.77%). SEC: M_w = 4388, M_n = 4258, PDI = 1.03.

Example 82

Synthesis of l,3-di(Myr-[G2]-PGLSA)₂-glycerol

0.47 g (0.16 mmol) of 2-benzyl-l,3-di(Myr-[G2]-PGLSA)₂-glycerol was dissolved in 20 mL of TΗF and 0.5 g of 10% Pd/C was added. The solution was then placed in a Parr tube on a hydrogenator and shaken under 50 psi H₂ for 10 hours. The solution was then filtered over wet celite, rotoevaporated, to yield the product.

Example 83

Synthesis of bz-SA-[G2]-PGLSA-TBDPS

0.77 g (0.99 mmol) of compound HO-[G2]-PGLSA-TBDPS was dissolved in 75 mL of CH₂Cl₂ with 0.99 g (4.76 mmol) of benzylated succinic acid (bz-sa), 0.58 g (1.98 mmol) of

DPTS, and 1.23 g (5.91 mmol) of DCC. The reaction was stirred at RT for 16 hours. The

DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in a minimum of CH₂Cl₂, cooled to 10 ⁰C for 1 hour and filtered. The solution was concentrated under reduced pressure and purified by column chromatorgraphy (30-50%

EtOAc in hexanβs) to afford 1.21 g of product (79% yield). R_f = 0.18 (40% EtOAc in hexanes). ¹H NMR (CDCl₃): δ 1.08 (s, 9H, t-butyl), 2.55-2.81 (m, 28H, succinic -CH₂- CH₂), 4.06-4.37 (m, 12Η, -CH₂-CH-CH₂-), 5.11 (s, 8Η, benzyl -CH₂-), 5.18-5.29 (m, 3Η, -

CH₂-CH-CH₂-), 7.22-7.44, 161-1.61 (m, 3OH, aromatic CH) ppm. ¹³C NMR (CDCl₃): δ 19.13, 26.81, 28.42, 28.64, 28.70, 28.91, 29.07, 30.56, 62.68, 66.72, 69.07, 73.69, 127.68,

128.23, 128.54, 130.06, 131.73, 135.21, 135.77, 171.64, 171.73, 171.90 ppm. FAB-MS:

1539.6 m/z (MH⁺) (theory: 1539.7 m/z (M⁺)). Elemental analysis: C, 63.35%; H, 6.02% (theory: C, 63.19%; H, 5.89%).

Example 84

Synthesis of bz-SA-[G2]-PGLSA-acid

1.12 g (0.73 mmol) of bz-SA-[G2]-PGLSA-TBDPS was dissolved in 100 mL of THF. Next, 0.89 g (2.76 mmol) of tetrabutylammonium fluoride trihydrate was added to the solution. The mixture was stirred at RT for 1 hour. After one hour the reaction was complete as indicated by TLC. The solution was diluted with 25 mL of H₂O and acidified with IN HCl to a pH of 3. The product was extracted into EtOAc, dried over Na₂SO₄, rotoevaporated and dried on the vacuum line. The product was purified by column chromatography (0-3% MeOH in CH₂Cl₂) to afford 0.71 g of product (75% yield). R_f = 0.18 (3% MeOH in CH₂Cl₂). ¹H NMR (CDCl₃): δ 2.54-2.69 (m, 28H, -CH₂-CH₂), 4.11- 4.31 (m, 12Η, -CH₂-CH-CH₂-), 5.09 (s, 8Η, benzyl -CH₂-), 5.18-5.25 (m, 3Η, -CH₂-CH- CH₂-), 7.25-7.36 (m, 2OH, aromatic CH) ppm. ¹³C NMR (CDCl₃): δ 28.57, 28.78, 28.94, 62.28, 62.43, 66.60, 69.16, 69.37, 128.24, 128.29, 128.61, 128.57, 171.33, 171.79, 171.95 ppm. FAB-MS: 1301.5 m/z (M-H⁺) (theory: 1301.3 m/z (M⁺)). Elemental analysis: C, 60.23%; H, 5.81% (theory: C, 60.00%; H, 5.58%). SEC: M_w = 1415, M_n = 1379, PDI = 1.03.

Example 85 Synthesis of bz-SA-[G4]-PGLSA-TBDPS

0.07 g (0.08 mmol) of compound HO-[G2]-PGLSA-TBDPS was dissolved in 40 mL of CH₂Cl₂ with 0.53 g (0.41 mmol) of bz-SA-[G2]-PGLSA-acid, 0.05 g (0.17 mmol) of DPTS, and 0.11 g (0.51 mmol) of DCC. The reaction was stirred at RT for 48 hours. The DCU precipitate was filtered and the solution was evaporated. The residue was resuspended in a minimum of CH₂Cl₂, cooled to 10 ⁰C for 1 hour and filtered. The solution was concentrated under reduced pressure and purified by column chromatorgraphy (30-80% EtOAc in hexanes) to afford 0.40 g of product (80% yield). R_f = 0.18 (65% EtOAc in hexanes). ¹H NMR (CDCl₃): δ 1.07 (s, 9H, t-butyl), 2.53-2.81 (m, 124H, succinic -CH₂- CH₂), 4.10-4.31 (m, 60Η, -CH₂-CH-CH₂-), 5.09 (s, 32Η, benzyl -CH₂-), 5.18-5.28 (m, 15Η, -CH₂-CH-CH₂-), 7.25-7.41, 7.45-7.49, 7.61-7.66 (m, 9OH, aromatic CH) ppm. ¹³C NMR (CDCl₃): δ 26.72, 28.52, 28.73, 28.87, 62.15, 66.43, 68.84, 69.16, 125.91, 127.64, 128.11, 128.33, 128.46, 130.01, 135.16, 135.66, 171.25, 171.54, 171.64, 171.81 ppm. MALDI-MS: XXX m/z (MH⁺) (theory: XXX m/z (M⁺)). Elemental analysis: C, 60.70%; H, 5.74% (theory: C, 60.34%; H, 5.63%). SEC: M_w = 5142, M_n = 5064, PDI = 1.02.

Example 86

Synthesis of bz-SA-[G4]-PGLSA-acid 0.22 g (0.04 mmol) of bz-SA-[G4]-PGLSA-TBDPS was dissolved in 12 mL of THF. Next, 0.04 g (0.13 mmol) of tetrabutylammonium fluoride trihydrate was added to the solution. The mixture was stirred at RT for 4 hours. The solution was diluted with 5 mL of H₂O and acidified with IN HCl to a pH of 3. Additional THF was added dropwise to keep product in solution. The product was extracted into EtOAc, dried over Na₂SO₄, rotoevaporated and dried on the vacuum line. The product was purified by column chromatography (20-100% EtOAc in hexanes) to afford the product. ¹H NMR (CDCl₃): δ 2.46-2.84 (m, 124H, -CH₂- CH₂), 4.12-4.49 (m, 60Η, -CH₂-CH-CH₂-), 5.02-5.36 (m, 57Η, benzyl -CH₂- and -CH₂- CH-CH₂-), 7.25-7.48 (m, 8OH, aromatic CH) ppm. ¹³C NMR (CDCl₃): δ 28.79, 28.93, 62.21, 66.51, 69.24, 127.64, 128.17, 128.52, 135.69, 171.34, 171.73, 171.91 ppm.

Example 87

General procedure for preparation of TiO₂ nanoparticles

There are several methods for the preparation Of TiO₂ nanoparticles in the literature. The procedure by Nussbaumer is adequate. Experimental details for TiO₂ synthesis can be found in Nussbaumer et al. Macromol. Mater. Eng., 2003, 288, 44. Notably, the TiO₂ nanoparticles reported by Nussbaumer et al. tend to aggregate and precipate at pΗ 7, i.e., the TiO₂ nanoparticles are not dispersed at pΗ 7. However, optical clear solutions of TiO₂ nanoparticles may be obtained at high pH and low pH. Example 88

General Procedure for preparation of hybrid organic-inorganic TiO₂ nanoparticles

Methoxy-Silane Pathway A sample of the above titanium dioxide material was neutralized to a pH >7, which causes the precipitation of the nano particles into a gel-like material. The material was washed with excess water to remove residual soluble salts. The resulting solids were then suspended in DMSO (dimethyl sulfoxide) and acidified with HCl to redissolve the nano particles, (note: nanoparticles of TiO₂ can be precipitated via neutralization, then redissolved acidic solutions-including water and alcohols. Aprotic solvents may minimize undesired Si-O-Si bond formation). Once the solution becomes clear, the 3- aminopropyltrimethoxysiloxane was added to the solution at elevated temperature and reduced pressure to remove water, methanol/ethanol, and HCl. The reaction is deemed complete when the reaction stops producing overhead. (The HCl is also consumed by the animogroup to maintain the charge density on the particle to keep them stable).

The solution can be used as a solution in DMSO for the IOL. DMSO is "inert" in vivo and has been used for 40 years as a therapeutic chemical to promote healing and joint pain. The DMSO will just leave the lens with time. Alternatively, the DMSO can be removed and the nanoparticles resuspended in aqueous solution

Chloro-Silane pathway

An alternative method is to utilize a substituted chloro silane in DMSO to liberate HCl as the only by-product. Possible chlorosilanes include trichloro(2-cyanoethyl)silane or trichloro(2-cyanopropyl)silane, then oxidation of the cyano to an acid.

Example 89 Stability of TiO₂ nanoparticles at pH 7 and pH 3.

The titanium nanoparticles as prepared from the literature method maintain optical clarity at pH <3 in air for months. Increasing the pH to ~5 or above results in precipitation of the titanium dioxide nanoparticles as a gel like material. As long as the material remains hydrated the particle integrity remains intact and can be brought back up into acidified aqueous or alcohol solutions (pH <3). Optically clear solutions are generally not obtainable at neutral pH or a physiological pH of between 5.5 and 8.5. Drying the neutralized solids in the oven results in a material that will not go back into solution. (Note: redissolving the solids in acidified acetonitrile produces a clear solution with a sticky insoluble material stuck to the glass. We have shown that the clear solution of acetontrile contained TiO₂ by neutralization and re-precipitation of the dissolved TiO₂. The new crop of solid had much more of a powder like consistency. It could be that we have selectively removed amorphous TiO₂ from the rutile material.)

Example 90

Preparation of Titanium Dioxide Nanoparticles. The basic procedure from Macromol. Mater. Eng. 2003, 288, 44-49 was utilized for the preparation of titanium dioxide with a 2-5 nm particle size. A 250 mL three-neck round bottom flask was charged with 70 mL of water, 14 mL of concentrated hydrochloric acid (37.4 wt % HCl), and a stir bar. The flask was then fitted with a reflux condenser, a pressure equalizing dropping funnel and a rubber septum. The flask was then cool to 0 ⁰C and 14 mL of titanium tetrachloride was charged to the pressure equalizing funnel. With vigorous stirring, the TiCl₄ was then added to the dropwise to the flask over a 30 minute period. At times during the addition, a yellow solid collected at the liquid-air interface of the flask. The flask was periodically manually shaken to facilitate the dissolution of the yellow solid. After the TiCl₄ addition was complete, the funnel was removed, then the reaction was heated to 60 ⁰C for one hour. The resulting solution was both optical clear and optically colorless. Upon standing for one week with exposure to air, the solution developed a distinct yellow color. This does not appear to happen when the solution is maintained in an oxygen free atmosphere. This solution contains 9.25 wt % TiO₂ and -22.5 wt % HCl. The refractive index of the solution was 1.4191. The refractive index of a 22.5 wt % HCl solution is 1.38, which indicates that the increase in RI is due to the TiO₂.

Example 91

Neutralization of the Titanium Dioxide Nanoparticles.

30 mL of the titanium dioxide solution, as prepared above, was neutralized with a saturated solution of sodium carbonate. As the HCl is reacted out of the solution, the TiO₂ begins to precipitate out of solution at the point where the sodium carbonate hits the solution. Continued stirring redissolves the material as long as the pH is below 5. When the pH began to raise above 5, the TiO₂ began to precipitate out of solution and remain as a solid. When the pH is brought to 7, the material turns into a sol gel. Sodium carbonate was added until the pH was -10. This material was transferred to a glass fritted funnel and was washed with copious amounts of water to remove the water soluble sodium salts.

If these solids are maintained moist, then they will go back up into solution when the solution is acidified with HCl to a pH of <4-5. If the solids are washed with methanol and dried in vacuo over night, then resulting solids will not completely dissolve with the addition of concentrated HCl and heating to 70 ⁰C.

Example 92

Lactic acid Modified Titanium Dioxide Nanoparticles for pH 7 stability.

1 gram of the neutralized sol gel (not washed with water) from example 91 was placed in a 20 niL vial along with a stir bar. The vial was placed in a 75 ⁰C bath, then 0.5 mL of DI water and 0.5 mL of 85 wt % lactic acid were added to the reaction mixture. The reaction was maintained at 75 ⁰C for 2.5 hours, which resulted in a slightly cloudy solution. The solution was partially neutralized with 80 mg of solid sodium carbonate. After stirring for an additional 10 minutes, the solution was optically clear and colorless. The solution pH can then be raised to at least 10 and no precipitation of the titanium dioxide occurs.

Example 93

Reaction of N,l-(3-trimethoxysilylpropyl)diethylene triamine with 1 Equivalent of Glycidol

A 100 mL flask was charged with a stir bar, 30 mL of anhydrous diethyl ether, and 5.00 mL of N,l-(3-trimethoxysilylpropyl)diethylene triamine (Aldrich), which caused the solution to become slightly cloudy. 1.29 mL of glycidol (Aldrich) was added dropwise to the solution over a 30 minute period. The reaction was allowed to stir for 4 hours. During this time, no additional solids were observed in the reaction flask. The diethyl ether was then removed on a rotovap to yield 5.63 grams of a viscous oil. The oil was then dissolved in enough methanol to yield a solution with 41 wt % of the product in methanol. This solution was used without further purification. Example 94

Reaction of N,l-(3-trimethoxysilyIpropyl)diethyIene triamine with 4 Equivalents of Glycidol.

A 100 mL flask was charged with a stir bar, 30 mL of anhydrous diethyl ether, and 6.00 mL of N,l-(3-trimethoxysilylpropyl)diethylene triamine (Aldrich), which caused the solution to become slightly cloudy. 6.2 mL of glycidol (Aldrich) was added dropwise to the solution over a 30 minute period. A temperature increase of ~5 ⁰C was observed over the addition. Solids began to develop in the reaction 15-20 minutes after the glycidol addition was complete. By one hour, a mass of solids had formed on the bottom of the reaction flask and the reaction stopped stirring. The reaction was allowed to stand over night, and then the solvent was poured out of the reaction flask. The resulting solids was extremely hard and could not be taken out of the flask. Methanol was added to the flask along with another stir bar. After stirring overnight, the solids dissolved into the methanol. The solution was determined to contain 40 wt % solids. This solution was used without additional purification.

Example 95

Coating of Titanium Dioxide Nanoparticles.

A 20 mL vial was charge with 1.0 mL of the solution prepared in Example 90 and a stir bar. The vial was then capped with a rubber septum. 1.0 mL of the solution prepared in

Example 93 was added dropwise to the vial over a 5 minute period. The solution was stirred at ambient temperature for two hours. A sample was removed and neutralized with a saturated sodium carbonate solution, which led to a clear, coagulated material. The original reaction mixture was placed in a 70 ⁰C bath for 4 hours. The solution was cooled to ambient temperature and subsequently neutralized with a saturated sodium carbonate solution. This again led to a coagulated gel. Water (4 mL) was added to the reaction vial, and the vial was heated to 70 ⁰C. After 1 hour, the reaction mixture was optically clear and colorless, except for a slight amount of microcrystalline material. The solution was cooled to ambient temperature, and the solids were removed by filtering through celite to provide a clear, colorless solution at neutral pH. Example 96

Coating Titanium Dioxide Nanoparticles.

A 20 niL vial was charged with 2.0 niL of the solution prepared in Example 90 and a stir bar. The vial was then capped with a rubber septum. 1.0 mL of the solution prepared in Example 95 was added dropwise to the vial over a 30 minute period. The solution was stirred at ambient temperature for two hours. A 1 mL sample was removed and neutralized to a pH of ~7 with a saturated sodium carbonate solution, which gave a slightly hazy, but colorless, solution. The remaining original reaction mixture was placed in a 70 ⁰C bath for 2 hours. Then, the solution was cooled to ambient temperature, and subsequently neutralized to a pH of ~7 with a saturated sodium carbonate solution. The resulting solution was optically clear and slightly yellow.

Example 97

Preparation of a Non-covalently Crosslinked Gel/Network Using (didodecane methyl amine)₂-PEG

The (didodecane methyl amine)₂-PEG was prepared in two steps by first treating

(NEb)-PEG with 8 equivalents of bromododecane, 15 equivalents of NaCO₃ in reflux ethanol to obtain (didodecane amine)₂-PEG. The (didodecane amine)₂-PEG, 1, was then treated with methyl iodine to afford (didodecane methyl amine)₂-PEG after precipitation in ether.

This cationic-hydrophobic linear polymer should form a gel with carboxyl- terminated dendritic polymers.

Example 98 General Procedure for the Preparation of a Hydrogel Through Photocrosslinking ([GI]-PGLSA-MA)₂-PEG

Five μL of solution containing 0.5% EY in HEPES buffer (0.1 M, 7.4 pH), 100 μL of 5.0 M

TEA, and 1 μL of VP were mixed with 2 mL of a 55 % w/v solution of the dendritic polymer in HEPES buffer. Upon laser exposure (argon ion laser, X_m3x = 488 and 514 nm, 200 mW) for 60 s, the pink viscous liquid crosslinked into a clear, soft, flexible hydrogel. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties. The crosslinked process can be with a UV or visible light system.

Example 99

General Procedure for the Preparation of a Hydrogel Through Photocrosslinking [G3]-PGLSA-MA

Gels were prepared by dissolving [G3]-PGLSA-MA, DMPA, and VP (1,000:10:1 respectively) in CH₂Cl₂. The polymer solution was exposed to UV light from a UVP BLAK-RAY long wave ultraviolet lamp for 5 minutes. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties. The polymer may be crosslinked with a UV or visible light absorbing system.

Example 100

General Procedure for the Preparation of a Hydrogel Through Photocrosslinking MA- [G3]-PGLSA-PEG-OMe

Five μL of a solution of 0.5% EY in HEPES buffer (0.1 M, 7.4 pH), 100 μL of 5.0 M TEA, and 1 μL of VP were mixed with 2 mL of a 55 % w/v solution of the dendritic polymer in HEPES buffer. Upon laser exposure (argon ion laser, λ_max = 488 and 514 nm, 200 mW) for 60 s, the pink viscous liquid crosslinked into a clear, soft, flexible hydrogel. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties. The polymer may be crosslinked with a UV or visible light absorbing system.

Example 101

General Procedure for the Preparation of a Hydrogel Through Treatment of LysLys(Lys)OMe with ([GI]-PGLSA-MA)₂-PEG

A gel was prepared by mixing an aqueous solution of the LysLys(Lys)OMe dendron with the ([GI]-PGLSA-MA)₂-PEG. For example, the dendron dissolved at 33% w/w in phosphate buffer pH=8.2 (10 mg dendron in 20 μl) and the ([G1]-PGLSA-MA)₂-PEG was dissolved at 50% w/w (50 mg ([G1]-PGLSA-MA)₂-PEG in 50 μL) in the same buffer. These two solutions were mixed together to provide a gel. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties.

Example 102

General Procedure for the Preparation of a Hydrogel Through Treatment of LysLys(Lys)OMe with PEG n-hydroxysuccinimide ((NHS)₂-PEG) A gel was prepared by mixing an aqueous solution of the LysLys(Lys)OMe dendron with (NHS)₂-PEG. For example, the dendron dissolved at 33% w/w in phosphate buffer pH=8.2 (10 mg dendron in 20 μl) and the (NHS)₂-PEG (commercially available, Mw = 3400) was dissolved at 55% w/w (50 mg PEG diNHS in 40 μL) in the same buffer. These two solutions were mixed together to provide a gel. Gelation was over in a few minutes. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties.

Example 103

General Procedure for the Preparation of a Hydrogel Through Treatment of LysLys(Lys)OMe with PEG dimaleimide ((MAL)₂-PEG)

A gel was prepared by mixing an aqueous solution of the LysLys(Lys)OMe dendron with (MAL)₂-PEG. For example, the dendron dissolved at 33% w/w in phosphate buffer pH=8.2 (10 mg dendron in 20 μl) and the PEG dimaleimide (commercially available, Mw = 3400) was dissolved at 55% w/w (50 mg PEG dimaleimide in 40 μL) in the same buffer. These two solutions were mixed together to provide a gel. Gelation occurs over 15 minutes. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties. Example 104

General Procedure for the Preparation of a Hydrogel Through Treatment of LysLys(Cys)Lys(CysLys(Cys))OMe^«HCl with PEG dialdehdye ((CHO)₂-PEG) or (dialdehyde succinic ester)₂-PEG A gel was prepared by mixing an aqueous solution of the CysLys(Cys)Lys(CysLys(Cys))OMe^«4HCl dendrons with the peg-dialdehyde or (dialdehyde succinic ester)₂-PEG. For example, the dendron dissolved at 33% w/w in phosphate buffer pH=7 (10 mg dendron in 20 μl), and the PEG compound was dissolved at 55% w/w (50 mg PEG in 40 μl) in the same buffer. These two solutions were mixed together to provide a gel. Gelation occurs almost immediately. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties.

Example 105 General Procedure for the Preparation of a Hydrogel Through Treatment of CysLys(Cys)Lys(CysLys(Cys))OMe»4HCl with (NHS)₂-PEG

A gel was prepared by mixing an aqueous solution of the CysLys(Cys)Lys(CysLys(Cys))OMe^«4HCl dendrons with the PEG(NHS)₂. For example, the dendron dissolved at 33% w/w in phosphate buffer pH=7 (10 mg dendron in 20 μl) and the PEG compound was dissolved at 55% w/w (50 mg PEG in 40 μl) in the same buffer. These two solutions were mixed together to provide a gel. Gelation occurs almost immediately. This reaction can be performed under a variety of concentrations of polymer to prepare gels with different physical and mechanical properties.

Example 106

General Procedure for the Preparation of a Hydrogel Through the Formation of Disulfide Bonds

A gel was prepared by allowing a solution of 22 mg of CysLys(Cys)Lys(CysLys(Cys))OMe*4HCl in 40 μL in phosphate buffered solution to rest for one week. The solution forms a weak hydrogel. 2006/023723

Example 107

Mechanical Properties of Hydrogel Lens Preparation Through Treatment of CysLys(Cys)Lys(CysLys(Cys))OMe»4HCl with (NHS)₂-PEG (3400 Mw), (NHS)₂-PEG (10000 Mw), or (NHS)₂-PEG (20000 Mw)

The gel was prepared by mixing an aqueous solution of the CysLys(Cys)Lys(CysLys(Cys))OMe»4HCl dendrons with the PEG-(NHS)₂ of the specified molecular weight. For example, the dendron dissolved in phosphate buffer pH=7 and the PEG-(NHS)₂ compound was dissolved in the same buffer. The two solutions were mixed together to provide a gel. Gelation occurs almost immediately. The three biodendritic polymers were selected because they span a range of biodendrimer compositions and structures and possess mechanical properties of a young natural functional lens (200 - 1000 Pa). Cylindrical constructs of the photocrosslinked hydrogels were prepared and evaluated for their compressive and shear properties on a dynamic mechanical spectrometer. Results are described in the Table 1 below. The Peg 20000 formulation with the CysLys(Cys)Lys(CysLys(Cys))OMe^»4HCl dendron affords a hydrogel with mechanical properties similar to that of a natural lens.

Table 1. Young's Modulus (kPa) for various PEG gels

Example 108

Nanoparticles dispersed in a PEG3400-SPA/Dendron Hydrogel A 4.7mg sample of dendron CysLys(Cys)Lys(CysLys(Cys))OMe«4HCl was dissolved in 129 μL of solution from Example 96 (pH 8-8.5, RI 1.387), and a second sample of 36 nig of Polyethylene Glycol - Succinimidyl Proprionic Acid (PEG3400-SPA) was dissolved in 101 μL of the same solution producing a milky white liquid. The two samples were mixed while stirring, and gelled within 11 seconds. The gel was an opaque, white solid with many air bubbles trapped inside the matrix. A small amount of BSS solution was placed on top of the gel, and after 24 hr the gel became clear and bubble free with a slight yellow color. The experiment was replicated.

Example 109

Nanoparticles dispersed in a PEG3400-BA/Dendron Gel In a centrifuge vial, 4.6 mg of dendron CysLys(Cys)Lys(CysLys(Cys))OMe«4HCl and 10 mg of sodium carbonate were weighed out, and subsequently dissolved in 128 μL of the solution from Example 92 (RI 1.413). A second sample was prepared by mixing 36 mg of polyethylene glyco!3400-butyraldehyde (PEG3400-BA) with 101 μL of the solution from example 92. The solutions were stirred and mixed together through a MixPac syringe, and then they were expelled into a mold. The gel was found to have an RI of 1.417, and transmission properties of 90%T for 400-800 nm and 0-10%T from 190-360 nm indicating good UV absorption.

Examples 110 Nanoparticle Crosslinked PEG-SPA Hydrogel

Sodium carbonate (10 mg) was weighed out in a centrifuge, and subsequently dissolved in 128 μL of the solution from Example 92 (RI 1.413). A second sample containing 36 mg of Polyethylene Glycol - Succinimidyl Proprionic Acid (PEG3400-SPA) was dissolved in 101 μL of buffer (PEG3400 refers to poly(ethylene glycol) with Mw = 3400 g/mol). Upon mixing the two solutions, a hydrogel was formed. The free amines that are on the surface of the coated TiO₂ particle reacted with the PEG-SPA to crosslinked a form a hydrogel network.

Incorporation by Reference All of the U.S. patents and U.S. patent application publications cited herein are hereby incorporated by reference. Equivalents

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

Claims

We Claim:

1. A lens composition comprising nanoparticles and a non-reversible hydrogel.

2. The composition of claim 1, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule.

3. The composition of claim 2, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

4. The composition of claim 2, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule formed by treating a dendrimeric compound of formula Ia or formula Ib with a polymerization agent selected from the group consisting of ultraviolet light, visible light, compound II, compound III, compound IV, and compound V; wherein formula Ia is represented by:

A¹— X¹-B— X¹— A²

Ia wherein

A is alkyl, aryl, aralkyl, -Si(R )3, or

A³ represents independently for each occurrence alkyl, cycloalkyl, heteroalkyl, heterocycloalkyl, aryl, heteroaryl, or aralkyl;

Y¹ represents independently for each occurrence R⁴, A⁴,

Z¹ represents independently for each occurrence -X¹ -R⁴ , E₅ or

Y² represents independently for each occurrence R⁵, A⁴,

Z represents independently for each occurrence -X 1 - rR.5 , E, or

Y³ represents independently for each occurrence R⁶, A ,

Z represents independently for each occurrence -X 1 - τR.6 , E, or

Y⁴ represents independently for each occurrence R⁷, A⁴,

Z represents independently for each occurrence -X 1 - τR>7 , E, or

Y represents independently for each occurrence R , A ,

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y⁶ represents independently for each occurrence R⁹, A ,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R represents independently for each occurrence H, alkyl, -OH, -N(R ICk )₂, -SH, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R³ represents independently for each occurrence alkyl, aryl, or aralkyl; R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ are H;

R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹ \, -SH, alkyl, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is O, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5; X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-;

X³ represents independently for each occurrence O, N(R¹⁰), or C(R¹⁵)(CO₂R¹⁰);

A⁴ represents independently for each occurrence

E represents independently for each occurrence

provided that R⁴ only occurs once, R⁵ only occurs once, R⁶ only occurs once, R⁷ only occurs once, R⁸ only occurs once, and R⁹ only occurs once; said formula Ib is represented by:

Ib or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X represents independently for each occurrence O or -N(R )-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH,

C(O)(C(R¹⁹)₂)_hSH, -CO₂(C(R^I9)₂)_hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH,

R¹⁸ represents independently for each occurrence H or alkyl;

R¹⁹ represents independently for each occurrence H, halogen, or alkyl;

II wherein

R^1"11 represents independently for each occurrence H or R^5~"

R^2"11 represents independently for each occurrence H or alkyl;

R^3"11 represents independently for each occurrence H, halogen, or alkyl;

R^4"11 represents independently for each occurrence alkyl, aryl, or aralkyl; and

R >5-II represents independently for each occurrence H or and z represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; said compound III is represented by:

III wherein R¹-¹¹¹ is -(C(R²-^m)₂)_xC(O)H, -C(O)(C(R²-^πi)₂)_yC(O)H, -(C(R²-^πi)₂)_xC(O)R ,^J3--^mπi, or -

C(O)(C(R²-^Iπ)₂)_yC(O)R³-^m;

R^2"111 represents independently for each occurrence H, alkyl, or halogen; I ,T3-i^mn is fluoroalkyl, chloroalkyl, -CH₂NO₂, or

B ,i-iπ is alkyl diradical, heteroalkyl diradical, x represents independently for each occurrence 0, 1, 2, 3, 4, 5, 6, 7, or 8;

y represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8;

v represents independently for each occurrence 2, 3, or 4; and

w is an integer in the range of about 5 to about 700, inclusive;

said compound IV is represented by:

A¹— X¹-B— X¹— A²

IV wherein

A is alkyl, aryl, aralkyl,r -Si(R )₃, or

Y¹ represents independently for each occurrence R ,

Z¹ represents independently for each occurrence -X¹ -R⁴, E, or

Y² represents independently for each occurrence R⁵,

Z² represents independently for each occurrence -X¹ -R⁵, E, or

Z represents independently for each occurrence -X ¹-R⁶ , E, or

Y⁴ represents independently for each occurrence R⁷,

Z⁴ represents independently for each occurrence -X¹-R⁷, E, or

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y represents independently for each occurrence R ,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R² represents independently for each occurrence H, alkyl, -OH, -N(R¹⁰)₂, -SH, hydroxyalkyl, or -[C(R^₂JdR¹⁶;

R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹ °)₂, -SH, alkyl, hydroxyalkyl, or -[C(R^₂]CiR¹⁶;

R¹² represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹³ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹⁴ represents independently for each occurrence H, alkyl, or -CO₂R¹⁰; R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰; R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence O, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is O₅ 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

X¹ and X² each represent independently for each occurrence O or -N(R¹⁰)-;

or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁶ represents independently for each occurrence O or -N(R³⁰)-; R²³ represents independently for each occurrence

R²⁴ represents independently for each occurrence H or alkyl;

R²⁵ represents independently for each occurrence H, halogen, or alkyl;

R²⁶ represents independently for each occurrence H or alkyl;

R²⁷ represents independently for each occurrence H, alkyl, or halogen;

R ,32 represents independently for each occurrenc

Z⁷ represents independently for each occurrence E¹ or

R ,33 represents independently for each occurrence

R i34 represents independently for each occurrence H, alkyl, or -CO₂R 30 ;.

E¹ represents independently for each occurrence H, -[C(R²⁴)₂]jC(O)H, or

p⁶ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p⁷ represents independently for each occurrence 0, 1, 2, 3, or 4; p⁸ represents independently for each occurrence 1, 2, or 3; p⁹ represents independently for each occurrence 0, 1, 2, or 3; n² and j each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; m¹ represents independently for each occurrence 1 or 2; v represents independently for each occurrence 2, 3, or 4; and w is an integer in the range of about 5 to about 700, inclusive.

5. The composition of claim 4, wherein said dendrimeric compound is compound of formula Ia, and said polymerization agent is ultraviolet light, visible light, compound II, or compound III.

m is 1 or 2. 7. The composition of claim 4, wherein A is

or -Si(R³)₃; wherein, m is 1 or 2.

8. The composition of claim 4, wherein Z¹ represents independently for each occurrence -

2. 9. The composition of claim 4, wherein Z² represents independently for each occurrence -

2.

10. The composition of claim 4, wherein Z³ represents independently for each

occurrence , and m is 1 or 2.

11. The composition of claim 4, wherein Z⁴ represents independently for each

12. The composition of claim 4, wherein Z⁵ represents independently for each

occurrence , and m is 1 or 2.

13. The composition of claim 4, wherein X¹ is O.

14. The composition of claim 4, wherein X¹ and X² are O.

15. The composition of claim 4, wherein n is 1.

16. The composition of claim 4, wherein p¹ is 2, 3, or 4.

17. The composition of claim 4, wherein p² is 1.

18. The composition of claim 4, wherein R¹ is H.

19. The composition of claim 4, wherein B

20. The composition of claim 4, wherein R¹ is H, B is A² is

21. The composition of claim 4, wherein R¹ is H, B is

23. The composition of claim 4, wherein R¹ is H, B is A² is

said polymerization agent is ultraviolet light or visible light.

24. The composition of claim 4, wherein R¹ is H, B is

25. The composition of claim 4, wherein R¹ is H, B is A² is

polymerization agent is compound in.

26. The composition of claim 4, wherein R¹ is H, B is A² i

27. The composition of claim 4, wherein R¹ is H, B is A² is

the Y groups

28. The composition of claim 4, wherein R¹ is H, B is A² is

, about 1/2 of the Y⁴ groups are H, about 1/2 of the

Y groups are and said polymerization agent is ultraviolet light or visible light.

29. The composition of claim 4, wherein R¹ is H, B is A² is

30. The composition of any one of claims 19-29, wherein p¹ is 1, 2, 3, or 4.

31. The composition of any one of claims 19-29, wherein p¹ is 2. 32. The composition of any one of claims 19-29, wherein p¹ is 4.

33. The composition of any one of claims 19-29, wherein m is 1.

34. The composition of claim 4, wherein B is ^x

35. The composition of claim 4, wherein R¹ is H, B is A² is

36. The composition of claim 4, wherein R¹ is H, B is A² is

37. The composition of claim 4, wherein R¹ is H, B is A² is

said polymerization agent is ultraviolet light or visible light.

39. The composition of claim 4, wherein R¹ is H, B is A^:

40. The composition of claim 4, wherein R¹ is H, B is A² is

polymerization agent is compound III.

41. The composition of claim 4, wherein R¹ is H, B is A² is

42. The composition of claim 4, wherein R¹ is H, B is A² is

43. The composition of any one of claims 34-42, wherein p¹ is 2.

44. The composition of any one of claims 34-42, wherein p¹ is 4. 45. The composition of any one of claims 34-42, wherein m is 1.

46. The composition of any one of claims 34-42, wherein R² is (Ci-C3)alkyl.

47. The composition of claim 4, wherein B is

48. The composition of claim 4, wherein R is H, B is

is 2.

49. The composition of claim 4, wherein R¹ is H, B is

50. The composition of claim 4, wherein R¹ is H, B is

51. The composition of claim 4, wherein R¹ is H, B is

polymerization agent is ultraviolet light or visible light. 52. The composition of claim 4, wherein R¹ is H, B is

53. The composition of claim 4, wherein R¹ is H, B is

54. The composition of claim 4, wherein R¹ is H, B is

Z¹ is

polymerization agent is ultraviolet light or visible light.

55. The composition of claim 4, wherein R¹ is H, B is

56. The composition of claim 4, wherein R¹ is H, B is

57. The composition of claim 4, wherein R¹ is H, B is

polymerization agent is ultraviolet light or visible light. 58. The composition of claim 4, wherein R¹ is H, B is

59. The composition of any one of claims 47-58, wherin w¹ is an integer in the range of about 50 to about 250.

60. The composition of any one of claims 47-58, wherein w¹ is an integer in the range of about 60 to about 90.

61. The composition of any one of claims 47-58, wherein p¹ is 2. 62. The composition of any one of claims 47-58, wherein m is 1.

63. The composition of any one of claims 47-58, wherein p¹ is 2, p² is 0, and R³ is (C₁- C₅)alkyl.

64. The composition of any one of claims 47-58, wherein p¹ is 2, p² is 0, R³ is (Ci- C₅)alkyl, and w¹ is an integer in the range of about 60 to about 90.

65. The composition of claim 4, wherein R¹ is H, B is A² is

R³ is alkyl, v² is 2, Y¹ is

66. The composition of claim 4, wherein R¹ is H, B A² is

R³ is alkyl, v² is 2, Y¹ is Z¹ is

67. The composition of claim 4, wherein R¹ is H, B is

68. The composition of claim 4, wherein R¹ is H, B A² is

R³ is alkyl, v² is 2, Y¹ is Z¹ is

69. The composition of claim 4, wherein R¹ is H, B A² is

, R³ is alkyl, v² is 2, Y¹ i is Z¹ is

polymerization agent is ultraviolet light or visible light.

70. The composition of claim 4, wherein R¹ is H, B A²

R³ is alkyl, v² is 2, Y¹ is Z¹ is

71. The composition of claim 4, wherein R¹ is H, B i A² is

R³ is alkyl, V² is 2, Y¹ is Z¹ is

72. The composition of claim 4, wherein R¹ is H, B is A² is

, R³ is alkyl, v² is 2, Y¹ i is

polymerization agent is ultraviolet light or visible light.

73. The composition of any one of claims 65-72, wherein p¹ is 2.

74. The composition of one of claims 65-72, wherein m is 1.

75. The composition of one of claims 65-72, wherein p¹ is 2, p² is 0, and R³ is (C₁- C₅)alkyl.

76. The composition of one of claims 65-72, wherein p¹ is 2, p² is 0, and R³ is (Ci- C₅)alkyl, and w² is an integer in the range of about 60 to about 90.

77. The composition of claim 4, wherein R¹ is H, B is , AMs

m is 1, or 2, Y¹ i is and Z¹ is

78. The composition of claim 4, wherein R¹ is H, B is

79. The composition of claim 4, wherein R¹ is H, B is is

The composition of claim 4, wherein R¹ is H, B is , A^z is

81. The composition of claim 4, wherein said polymerization agent is compound II. 82. The composition of claim 4, wherein said polymerization agent is compound III. 83. The composition of claim 4, wherein said polymerization agent is compound III, R^1"

III is -C(O)H, and R 2^-i^mπ is H.

84. The composition of claim 4, wherein said polymerization agent is compound III, R¹

III ; is -C(O)H, I >T2-i¹π" is H₃ and B l¹-III . 85. The composition of claim 4, wherein said polymerization agent is compound III, R 2-

¹¹¹ is -C(O)H, R²-¹¹¹ is H, B¹-¹¹¹ is - ^w , and w is an integer in the range of about 60-90.

86. The composition of claim 4, wherein said compound of formula Ia is

87. The composition of claim 4, wherein said dendrimeric compound is a compound of formula Ib.

88. The composition of claim 87, wherein v is 2.

89. The composition of claim 87, wherein X⁵ is -N(H)-.

90. The composition of claim 87, wherein R¹⁸ is H.

91. The composition of claim 87, wherein R¹⁹ is H. > 92. The composition of claim 87, wherein R²⁰ is H.

93. The composition of any one of claims 87-92, wherein w is an integer in the range of about 20-500.

94. The composition of any one of claims 87-92, wherein w is an integer in the range of about 40-250. 95. The composition of any one of claims 87-92, wherein w is an integer in the range of about 60-90.

96. The composition of claim 87, said compound of formula Ib is

97. The composition of claim 4, said polymerization agent is compound V.

98. The composition of claim 97, wherein v is 2.

99. The composition of claim 97, wherein X⁶ is -N(H)-.

100. The composition of claim 97, wherein R²⁴ is H.

101. The composition of claim 97, wherein R²⁵ is H.

102. The composition of claim 97, wherein R²⁶ is H.

103. The composition of any one of claims 97-102, wherein w is an integer in the range of about 20-500.

104. The composition of any one of claims 97-102, wherein w is an integer in the range of about 40-250. 105. The composition of any one of claims 97-102, wherein w is an integer in the range of about 60-90.

106. The composition of any one of claims 97-102, wherein R represents independently

for each occurrence

107. The composition of any one of claims 97-102, wherein R >23 represents independently

for each occurrence is E¹.

108. The composition of claim 97, said compound V is

109. The composition of claim 4, wherein said polymerization agent is ultraviolet light or visible light. 110. The composition of claim 4, wherein said polymerization agent is ultraviolet light.

111. The composition of claim 4, wherein said polymerization agent is light with a λ of 400-600 nm.

112. The composition of claim 4, wherein said polymerization agent is light with a λ of 450-550 nm.

113. The composition of claim 4, wherein said polymerization agent is light with a λ of 488-514 nm.

114. The composition of claim 2, wherein said non-reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VT with a polymerization agent represented by formula VII, wherein formula VT is represented by:

C(O)(C(R³)₂)_mSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

R² represents independently for each occurrence H or alkyl; R³ represents independently for each occurrence H, halogen, or alkyl; R⁴ represents independently for each occurrence alkyl, aryl, or aralkyl;

R⁵ represents independently for each occurrence -(C(R³)₂)_mSH, -C(O)(C(R³)₂)_mSH, -

R^1-vιι___B__R1-vιι

VII

wherein

R^1-vιι represents independently for each occurrence -(C(J ,c2-^"V ^vI ^K)₂)_XC(O)H, -C(O)(C(R' 2-

R^2-vιι represents independently for each occurrence H, alkyl, or halogen;

R^3-vιι is is fluoroalkyl, chloroalkyl, -CH₂

B is alkyl diradical, heteroalkyl diradical, v^2-vιι represents independently for each occurrence 2, 3, or 4; and w^2-vιι is an integer in the range of about 5 to 700, inclusive.

115. The composition of claim 114, w^2-vιι is an integer in the range of about 50 to about 250.

116. The composition of claim 114, w^2-vιι is an integer in the range of about 60 to about 90.

117. The composition of claim 114, wherein said polymerization agent is a compound of formula VII, R^2-vιι is -C(O)H, and R^2-vιι is H.

118. The composition of claim 114, wherein said polymerization agent is a compound of

formula VII, R ,2^z--V^vI^uI . is -C(O)H, R^2Λαi is H, B is and v^2' ^■VII is 2.

119. The composition of claim 114, wherein said polymerization agent is a compound of

formula VII₅ R^2-vιι is -C(O)H, R^2-vιι is H, B is

2, and w^2"vπ is an integer in the range of about 60-90.

120. The composition of claim 114, wherein n is 3, 4, or 5.

121. The composition of claim 114, wherein n is 4.

122. The composition of claim 114, wherein R² is H.

123. The composition of claim 114, wherein R³ is H.

124. The composition of claim 114, wherein R⁴ is alkyl.

125. The composition of claim 114, wherein R⁴ is methyl or ethyl.

126. The composition of claim 114, wherein n is 4, R² and R³ is H, and R⁴ is alkyl.

127. The composition of claim 114, wherein R¹ is

128. The composition of claim 114, wherein R¹ is and p is 1.

129. The composition of claim 114, wherein R¹

130. The composition of claim 114, wherein R¹ and p is 1.

131. The composition of claim 114, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

132. The composition of claim 114, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

1. 133. The composition of claim 114, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and a Bronstead acid.

134. The composition of claim 114, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and HA, wherein A is halogen or -O₂CR⁶, and R⁶ is alkyl, fluoroalkyl, aryl, or aralkyl. 135. The composition of claim 114, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and an acid selected from group consisting of HCl and HBr.

136. The composition of claim 114, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and HO₂CR⁶, wherein R⁶ is fluoroalkyl. 137. The composition of claim 114, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula VI and CF3CO2H.

138. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

139. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon-based nanoparticles.

140. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

141. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

142. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

143. The composition of any one of claims 1-4 or 114, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide. 144. The composition of any one of claims 1-4 or 114, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

145. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel. 146. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

147. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are present in about 1 to about 40 weight percent. 148. The composition of any one of claims 1-4 or 114, wherein said nanoparticles are present in about 5 to about 25 weight percent.

149. The composition of any one of claims 1-4 or 114, wherein the diameter of said microparticles is less than about 50 nm.

150. The composition of any one of claims 1-4 or 114, wherein the diameter of said microparticles is less than about 20 nm.

151. The composition of any one of claims 1-4 or 114, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

152. The composition of any one of claims 1-4 or 114, wherein said lens is transparent.

153. The composition of any one of claims 1-4 or 114, wherein said lens swells less than about 100% in aqueous solution.

154. The composition of any one of claims 1-4 or 114, further comprising a material that absorbs ultraviolet light.

155. The composition of any one of claims 1-4 or 114, wherein said composition has a sterility assurance level of at least about 10^"3. 156. The composition of any one of claims 1-4 or 114, wherein said composition has a sterility assurance level of at least about 10^~5.

157. The composition of any one of claims 1-4 or 114, wherein less than about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

158. The composition of any one of claims 1-4 or 114, wherein less than about 15% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

159. The composition of any one of claims 1-4 or 114, wherein less than about 5% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

160. The composition of any one of claims 1-4 or 114, wherein less than about 1% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond. 161. A lens composition comprising nanoparticles and a reversible hydrogel, wherein said hydrogel comprises a dendrimeric macromolecule.

162. The composition of claim 161, wherein said reversible hydrogel further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

163. The composition of claim 161, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VIII or formula IX with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formula VIII is represented by:

A¹— X¹-B— X¹— A²

VIII wherein

A is alkyl, aryl, aralkyl, -Si(R )₃, or

Y¹ represents independently for each occurrence R⁴,

Z¹ represents independently for each occurrence -X^:-R⁴ , E, or

Y² represents independently for each occurrence R⁵,

Z² represents independently for each occurrence -X¹ -R⁵, E, or

Y³ represents independently for each occurrence R⁶,

Z represents independently for each occurrence -X -R , E, or

Y⁴ represents independently for each occurrence R⁷,

Z⁴ represents independently for each occurrence -X¹-R⁷, E, or

Y represents independently for each occurrence R⁸,

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y represents independently for each occurrence R ,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R² represents independently for each occurrence H, alkyl, -OH, -N(R¹ °)₂, -SH, hydroxyalkyl, or -[C(R¹^_dR¹⁶;

R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹⁰)₂, -SH, alkyl, hydroxyalkyl, or -[C(R¹^]CiR¹⁶;

R¹² represents independently for each occurrence H, alkyl, aryl, or aralkyl;

R¹³ represents independently for each occurrence H, alkyl, aryl, or aralkyl;

R¹⁴ represents independently for each occurrence H, alkyl, or -CO₂R¹⁰;

R¹⁵ represents independently for each occurrence H, alkyl, or -OR¹⁰;

R¹⁶ represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl,

, 10- imidazolyl, indolyl, -N(R^IU)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R^1U)₂, or -C(NH₂)N(R^{1 ϋ})₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w¹ and w² each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is O, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

IX or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁵ represents independently for each occurrence O or -N(R²²)-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)i,SH,

R¹⁸ represents independently for each occurrence H or alkyl; R¹⁹ represents independently for each occurrence H, halogen, or alkyl; R²⁰ represents independently for each occurrence H or alkyl; R²¹ represents independently for each occurrence H, -(C(R¹⁹)2)_hSH, -

164. The composition of claim 163, wherein a compound of formula VIII contains at least two thiol groups.

165. The composition of claim 163, wherein a compound of formula VIII contains at least five thiol groups.

166. The composition of claim 163, wherein a compound of formula IX contains at least two thiol groups. 167. The composition of claim 163, wherein a compound of formula IX contains at least five thiol groups.

168. The composition of claim 163, wherein A¹ is

2. 169. The composition of claim 163, wherein A² is

Si(R³)3; wherein, m is 1 or 2.

170. The composition of claim 163, wherein Z¹ represents independently for each

occurrence -X¹ -R⁴ , and m is 1 or 2.

171. The composition of claim 163, wherein Z² represents independently for each

occurrence -X¹ -R⁵ 1 or 2.

172. The composition of claim 163, wherein Z³ represents independently for each

occurrence -X¹ -R⁶ or V x¹ , and m is 1 or 2.

173. The composition of claim 163, wherein Z represents independently for each

occurrence -X¹ -R⁷ or , and m is 1 or 2.

174. The composition of claim 163, wherein Z⁵ represents independently for each

occurrence -X¹ -R⁸ or and m is 1 or 2. 175. The composition of claim 163, wherein X¹ is O.

176. The composition of claim 163, wherein X¹ and X² are O.

177. The composition of claim 163, wherein n is 1.

178. The composition of claim 163, wherein p¹ is 2, 3, or 4.

179. The composition of claim 163, wherein p² is 1. 180. The composition of claim 163, wherein R¹ is H.

181. The composition of claim 163, wherein B

182. The composition of claim 163, wherein

183. The composition of claim 163, wherein R¹ is H, B is A² is

184. The composition of claim 163, wherein R¹ is H, B is

185. The composition of claim 163, wherein R¹ is H, B is

186. The composition of claim 163, wherein R¹ is H, B is A² is

of

the Y⁴ groups are 187. The composition of claim 163, wherein R¹ is H, B is A² is

188. The composition of any one of claims 181-187, wherein p¹ is 1, 2, 3, or 4.

189. The composition of any one of claims 181-187, wherein p¹ is 2.

190. The composition of any one of claims 181-187, wherein p¹ is 4. 191. The composition of any one of claims 181-187, wherein m is 1.

192. The composition of claim 163, wherein B

193. The composition of claim 163, wherein R 1 i .s H₅ B is A Λ2 is

194. The composition of claim 163, wherein R¹ is H, B is A is

195. The composition of claim 163, wherein R¹ is H, B is A² is

, Z¹ is

196. The composition of claim 163, wherein R¹ is H, B is , A² is

is

197. The composition of claim 163, wherein R¹ is H, B is A² is

198. The composition of any one of claims 192-197, wherein p¹ is 1, 2, 3, or 4. 199. The composition of any one of claims 192-197, wherein p¹ is 2.

200. The composition of any one of claims 192-197, wherein p¹ is 4.

201. The composition of any one of claims 192- 197, wherein m is 1.

202. The composition of any one of claims 192-197, wherein R² is (Ci-C₃)alkyl.

203. The composition of claim 163, wherein B is

204. The composition of claim 163, wherein R¹ is H, B is

2.

205. The composition of claim 163, wherein R¹ is H, B is

206. The composition of claim 163, wherein R¹ is H, B IS

207. The composition of claim 163, wherein R¹ is H, B is

208. The composition of claim 163, wherein R¹ is H, B is

209. The composition of claim 163, wherein R¹ is H, B is

210. The composition of claim 163, wherein R¹ is H, B is

211. The composition of claim 163, wherein R¹ is H, B is

212. The composition of any one of claims 203-211, wherin w¹ is an integer in the range of about 50 to about 250. 213. The composition of any one of claims 203-211, wherein w¹ is an integer in the range of about 60 to about 90.

214. The composition of any one of claims 203-211, wherein p¹ is 2.

215. The composition of any one of claims 203 -211 , wherein m is 1.

216. The composition of any one of claims 203-211, wherein p¹ is 2, p² is 0, and R³ is (Ci-C₅)alkyl.

217. The composition of any one of claims 203-211, wherein p¹ is 2, p² is 0, R³ is (C₁- Cs)alkyl, and w¹ is an integer in the range of about 60 to about 90.

218. The composition of claim 163, wherein R¹ is H, B A² is

R³ is alkyl, v² is 2, Y¹ is Z¹ IS

219. The composition of claim 163, wherein R¹ is H, B is A² is

R³ is alkyl,v² is 2, Y¹ is

220. The composition of claim 163, wherein R¹ is H, B is

221. The composition of claim 163, wherein R¹ is H, B A² is

R³ is alkyl, v² is 2, Y¹ is IS

222. The composition of claim 163, wherein R¹ is H, B A² is

, R³ is alkyl, v² is 2, Y¹ is Z¹ IS

223. The composition of claim 163, wherein R¹ is H, B is A² is

Z¹ is

224. The composition of any one of claims 218-223, wherein p¹ is 2. 225. The composition of any one of claims 218-223, wherein m is 1.

226. The composition of any one of claims 218-223, wherein p¹ is 2, p² is 0, and R³ is (Ci-C₅)alkyl.

227. The composition of any one of claims 218-223, wherein p¹ is 2, p² is 0, and R³ is (C₁-C₅)alkyl, and w² is an integer in the range of about 60 to about 90.

228. The composition of claim 163, wherein R¹ is H, B is A² i IS

229. The composition of claim 163, wherein R¹ is H, B is A² is

230. The composition of claim 163, wherein R¹ is H, B is

231. The composition of claim 163, wherein R¹ is H, B is A² is

232. The composition of claim 163, wherein said dendrimeric molecule is

233. The composition of claim 163, wherein said dendrimeric compound is a compound of formula IX.

234. The composition of claim 233, wherein v is 2.

235. The composition of claim 233, wherein X⁵ is -N(H)-.

236. The composition of claim 233, wherein R¹⁸ is H.

237. The composition of claim 233, wherein R¹⁹ is H. 238. The composition of claim 233, wherein R²⁰ is H.

239. The composition of any one of claims 233-238, wherein w is an integer in the range of about 20-500.

240. The composition of any one of claims 233-238, wherein w is an integer in the range of about 40-250. 241. The composition of any one of claims 233-238, wherein w is an integer in the range of about 60-90.

242. The composition of claim 163, said compound of formula IX is:

243. The composition of claim 242, wherein said oxidizing agent is O₂.

244. The composition of claim 163, wherein about 1% to about 70% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

245. The composition of claim 163, wherein about 5% to about 50% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

246. The composition of claim 163, wherein about 5% to about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

247. The composition of claim 161, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula X with an oxidizing agent sufficient to polymerize said compound of formula X, wherein formula X is represented by:

X or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

R¹ represents independently for each occurrence H, -(C(R³)₂)_mSH,

C(O)(C(R³) ₂)_mSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

n and m each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; and p is 1, 2, 3, 4, or 5. 248. The composition of claim 247, wherein said compound of formula X has at least two thiol groups.

249. The composition of claim 247, wherein said compound of formula X has at least five thiol groups.

250. The composition of claim 247, wherein n is 3, 4, or 5.

251. The composition of claim 247, wherein n is 4.

252. The composition of claim 247, wherein R² is H.

253. The composition of claim 247, wherein R³ is H.

254. The composition of claim 247, wherein R⁴ is alkyl.

255. The composition of claim 247, wherein R⁴ is methyl or ethyl.

256. The composition of claim 247, wherein n is 4, R² and R³ is H, and R⁴ is alkyl.

257. The composition of claim 247, wherein R¹ is

258. The composition of claim 247, wherein R¹ is and p is l.

259. The composition of claim 247, wherein R¹ is

260. The composition of claim 247, wherein R¹ is and p is 1.

261. The composition of claim 247, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

, and p is 1.

262. The composition of claim 247, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

263. The composition of claim 247, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and a Bronstead acid.

264. The composition of claim 247, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HA, wherein A is halogen or -O₂CR⁶, and R⁶ is alkyl, fluoroalkyl, aryl, or aralkyl.

265. The composition of claim 247, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and an acid selected from group consisting ofHCl and HBr.

266. The composition of claim 247, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HO₂CR⁶, wherein R⁶ is fluoroalkyl.

267. The composition of claim 247, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and CF3CO2H.

268. The composition of claim 247, wherein said oxidizing agent is O₂.

269. The composition of claim 247, wherein about 1% to about 70% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

270. The composition of claim 247, wherein about 5% to about 50% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

271. The composition of claim 247, wherein about 5% to about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

272. The composition of claim 161, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof. 273. The composition of claim 161, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

274. The composition of claim 161, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

275. The composition of claim 161, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

276. The composition of claim 161, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

277. The composition of claim 161, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

278. The composition of claim 161, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide. 279. The composition of claim 161, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

280. The composition of claim 161, wherein said nanoparticles are covalently bonded to said dendrimeric macromolecule.

281. The composition of claim 161, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

282. The composition of claim 161, wherein said nanoparticles are present in about 1 to about 40 weight percent.

283. The composition of claim 161, wherein said nanoparticles are present in about 5 to about 25 weight percent.

284. The composition of claim 161, wherein the diameter of said microparticles is less than about 50 nm.

285. The composition of claim 161, wherein the diameter of said microparticles is less than about 20 nm. 286. The composition of claim 161, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

287. The composition of claim 161, wherein said lens is transparent.

288. The composition of claim 161, wherein said lens swells less than about 100% in aqueous solution.

289. The composition of claim 161, further comprising a material that absorbs ultraviolet light.

290. The composition of claim 161, wherein said composition has a sterility assurance level of at least about 10^"3. 291. The composition of claim 161, wherein said composition has a sterility assurance level of at least about 10^"5.

292. A lens composition comprising nanoparticles and a reversible hydrogel, wherein said nanoparticles have a core made of a metal, metal sulfide, zeolite, ceramic, diamond, titanium dioxide, zinc oxide, aluminium oxide, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, carbon, or a combination thereof.

293. The composition of claim 292, wherein said reversible hydrogel comprises a dendrimeric macromolecule.

294. The composition of claim 292, wherein said reversible hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

295. The composition of claim 292, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VIII or formula IX with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formula VIII is represented by:

A¹— X¹-B— X¹— A²

VIII wherein

or

Y¹ represents independently for each occurrence R⁴,

Z¹ represents independently for each occurrence -X¹-R⁴ , E, or

Y² represents independently for each occurrence R⁵,

Z² represents independently for each occurrence -X ¹-R⁵, E, or

Y³ represents independently for each occurrence R ,

Z³ represents independently for each occurrence -X ¹-R⁶ , E, or

Y⁴ represents independently for each occurrence

Z represents independently for each occurrence -X¹-R⁷, E, or

Y⁵ represents independently for each occurrence R⁸,

Z⁵ represents independently for each occurrence -X¹ -R⁸, E, or

Y⁶ represents independently for each occurrence R⁹,

R¹ represents independently for each occurrence H, alkyl, or halogen;

R² represents independently for each occurrence H, alkyl, -OH, -N(R¹ °)₂, -SH, hydroxyalkyl, or -[C(R¹)₂]_dR¹⁶;

R¹⁰ represents independently for each occurrence H, alkyl, aryl, or aralkyl; R¹¹ represents independently for each occurrence H, -OH, -N(R¹⁰)₂, -SH, alkyl, hydroxyalkyl, or -[QR^J_dR¹⁶;

R > 16 represents independently for each occurrence phenyl, hydroxyphenyl, pyrrolidyl, imidazolyl, indolyl, -N(R¹⁰)₂, -SH, -S-alkyl, -CO₂R¹⁰, -C(O)N(R¹⁰)₂, or -C(NH₂)N(R¹⁰)₂; d represents independently for each occurrence 1, 2, 3, 4, 5, or 6; n represents independently for each occurrence 1, 2, 3, 4, 5, or 6; p¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7; or 8; p² represents independently for each occurrence 0, 1, 2, 3, or 4; p³ represents independently for each occurrence 1, 2, or 3; p⁴ represents independently for each occurrence 0, 1, 2, or 3; t represents independently for each occurrence 2, 3, 4, or 5 in accord with the rules of valence; v¹ and v² each represent independently for each occurrence 2, 3, or 4; w and w each represent independently for each occurrence an integer from about 5 to about 700, inclusive; x is 1, 2, or 3; y is 0, 1, 2, 3, 4, or 5; z¹ represents independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; z² and z³ each represent independently for each occurrence 1, 2, 3, 4, or 5;

or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein

X⁵ represents independently for each occurrence O or -N(R²²)-;

R¹⁷ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH, -

R¹⁸ represents independently for each occurrence H or alkyl; R¹⁹ represents independently for each occurrence H, halogen, or alkyl; R²⁰ represents independently for each occurrence H or alkyl; R²¹ represents independently for each occurrence H, -(C(R¹⁹)₂)_hSH,

C(O)(C(R¹⁹)₂)_hSH, -CO₂(C(R¹⁹)₂)_hSH, -C(O)N(R¹⁸)(C(R¹⁹)₂)_hSH, , or

296. The composition of claim 295, wherein a compound of formula Viπ contains at least two thiol groups.

297. The composition of claim 295, wherein a compound of formula VIII contains at least five thiol groups.

298. The composition of claim 295, wherein a compound of formula IX contains at least two thiol groups. 299. The composition of claim 295, wherein a compound of formula IX contains at least five thiol groups.

300. The composition of claim 295, wherein A¹ is

2. 301. The composition of claim 295, wherein A² is

Si(R³)₃; wherein, m is 1 or 2.

302. The composition of claim 295, wherein Z¹ represents independently for each

2.

303. The composition of claim 295, wherein Z² represents independently for each

occurrence and m is 1 or 2.

304. The composition of claim 295, wherein Z³ represents independently for each

occurrence -X¹ -R⁶ , and m is 1 or 2.

305. The composition of claim 295, wherein Z⁴ represents independently for each

occurrence -X¹ -R⁷ , and m is 1 or 2.

306. The composition of claim 295, wherein Z⁵ represents independently for each

2. 307. The composition of claim 295, wherein X¹ is O.

308. The composition of claim 295, wherein X¹ and X² are O.

309. The composition of claim 295, wherein n is 1.

310. The composition of claim 295, wherein p¹ is 2, 3, or 4.

311. The composition of claim 295, wherein p² is 1. 312. The composition of claim 295, wherein R¹ is H.

313. The composition of claim 295, wherein B is

314. The composition of claim 295, wherein R¹ is H, B is A² is

315. The composition of claim 295, wherein R¹ is H, B is ^² is

317. The composition of claim 295, wherein R¹ is H, B is A² is

318. The composition of claim 295, wherein R¹ is H, B is A² is

the Y⁴ groups are

319. The composition of claim 295, wherein R¹ is H, B is A² is

320. The composition of any one of claims 313-319, wherein p¹ is 1, 2, 3, or 4.

321. The composition of any one of claims 313-319, wherein p¹ is 2.

322. The composition of any one of claims 313-319, wherein p¹ is 4.

323. The composition of any one of claims 313-319, wherein m is 1.

324. The composition of claim 295 wherein B

325. The composition of claim 295, wherein R¹ is H, B is A² is

326. The composition of claim 295, wherein R¹ is H, B is A² is

327. The composition of claim 295, wherein R¹ is H, B is A IS

328. The composition of claim 295, wherein R¹ is H, B is A² is

329. The composition of claim 295, wherein R¹ is H, B is A² is

330. The composition of any one of claims 324-329, wherein p¹ is 1, 2, 3, or 4.

331. The composition of any one of claims 324-329, wherein p¹ is 2.

332. The composition of any one of claims 324-329, wherein p¹ is 4.

333. The composition of any one of claims 324-329, wherein m is 1.

334. The composition of any one of claims 324-329, wherein R² is (Ci-C₃)alkyl.

335. The composition of claim 295, wherein B IS

336. The composition of claim 295, wherein R¹ is H, B IS

2.

337. The composition of claim 295, wherein R¹ is H, B IS

338. The composition of claim 295, wherein R¹ is H, B is

339. The composition of claim 295, wherein R¹ is H, B is

340. The composition of claim 295, wherein R¹ is H, B is

341. The composition of claim 295, wherein R¹ is H, B i is

342. The composition of claim 295, wherein R¹ is H, B is

343. The composition of claim 295, wherein R¹ is H, B is

344. The composition of any one of claims 335-343, wherin w¹ is an integer in the range ofabout 50 to about 250. 345. The composition of any one of claims 335-343, wherein w¹ is an integer in the range of about 60 to about 90.

346. The composition of any one of claims 335-343, wherein p¹ is 2.

347. The composition of any one of claims 335-343, wherein m is 1.

348. The composition of any one of claims 335-343, wherein p¹ is 2, p² is 0, and R³ is (C_rC_s)alkyl.

349. The composition of any one of claims 335-343, wherein p¹ is 2, p² is 0, R³ is (C₁- C₅)alkyl, and w¹ is an integer in the range of about 60 to about 90.

350. The composition of claim 295, wherein R¹ is H, B is A ^Δz is

R³ is alkyl, v² is 2, Y¹ i is

351. The composition of claim 295, wherein R¹ is H, B is A² is

352. The composition of claim 295, wherein R¹ is H, B is

353. The composition of claim 295, wherein R¹ is H₅ B is A² is

, R³ is alkyl, v² is 2, Y¹ is

354. The composition of claim 295, wherein R¹ is H, B is

355. The composition of claim 295, wherein R¹ is H, B A² is

, R³ is alkyl, v² is 2, Y¹ is Z¹ IS

356. The composition of any one of claims 350-355, wherein p¹ is 2. 357. The composition of any one of claims 350-355, wherein m is 1.

358. The composition of any one of claims 350-355, wherein p¹ is 2, p² is 0, and R³ is (d-C₅)alkyl.

359. The composition of any one of claims 350-355, wherein p¹ is 2, p² is 0, and R³ is (C_\-Cs)a\kyl, and w² is an integer in the range of about 60 to about 90.

360. The composition of claim 295, wherein R¹ is H, B is A² is

, m is 1, or 2, Y¹ i is and Z¹ is

361. The composition of claim 295, wherein R¹ is H, B is A² is

The composition of claim 295, wherein R¹ is H, B is , A² is

363. The composition of claim 295, wherein R¹ is H, B is

364. The composition of claim 295, wherein said compound of formula VIII is

365. The composition of claim 295, wherein said dendrimeric compound is a compound of formula IX.

366. The composition of claim 365, wherein v is 2.

367. The composition of claim 365, wherein X⁵ is -N(H)-.

368. The composition of claim 365, wherein R¹⁸ is H.

369. The composition of claim 365, wherein R¹⁹ is H. 370. The composition of claim 365, wherein R²⁰ is H.

371. The composition of any one of claims 365-370, wherein w is an integer in the range of about 20-500.

372. The composition of one of claims 365-370, wherein w is an integer in the range of about 40-250. 373. The composition of one of claims 365-370, wherein w is an integer in the range of about 60-90.

374. The composition of claim 295, said compound of formula IX is:

375. The composition of claim 374, wherein said oxidizing agent is O₂.

376. The composition of claim 295, wherein about 1% to about 70% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

377. The composition of claim 295, wherein about 5% to about 50% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

378. The composition of claim 295, wherein about 5% to about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

379. The composition of claim 292, wherein said reversible hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula X with an oxidizing agent sufficient to polymerize said compound of formula X, wherein formula X is represented by:

X or a pharmaceutically acceptable salt, solvate, or hydrate thereof, wherein R¹ represents independently for each occurrence H

C(O)(C(R³)₂)_mSH, -CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH,

CO₂(C(R³)₂)_mSH, -C(O)N(R²)(C(R³)₂)_mSH, n and m each represent independently for each occurrence 1, 2, 3, 4, 5, 6, 7, or 8; and p is 1, 2, 3, 4, or 5. 380. The composition of claim 379, wherein said compound of formula X has at least two thiol groups.

381. The composition of claim 379, wherein said compound of formula X has at least five thiol groups.

382. The composition of claim 379, wherein n is 3, A, or 5.

383. The composition of claim 379, wherein n is 4.

384. The composition of claim 379, wherein R² is H.

385. The composition of claim 379, wherein R³ is H.

386. The composition of claim 379, wherein R⁴ is alkyl.

387. The composition of claim 379, wherein R⁴ is methyl or ethyl.

388. The composition of claim 379, wherein n is 4, R² and R³ is H, and R⁴ is alkyl.

389. The composition of claim 379, wherein R¹ is

390. The composition of claim 379, wherein R¹ is and p is 1.

391. The composition of claim 379, wherein R¹ is

392. The composition of claim 379, wherein R¹ is and p is 1.

393. The composition of claim 379, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

and p is 1.

394. The composition of claim 379, wherein n is 4, R² and R³ are H, R⁴ is methyl, R¹ is

395. The composition of claim 379, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and a Bronstead acid.

396. The composition of claim 379, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HA, wherein A is halogen or -O₂CR⁶, and R⁶ is alkyl, fluoroalkyl, aryl, or aralkyl.

397. The composition of claim 379, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and an acid selected from group consisting ofHCl and HBr.

398. The composition of claim 379, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and HO₂CR⁶, wherein R⁶ is fluoroalkyl.

399. The composition of claim 379, wherein said pharmaceutically acceptable salt is a complex formed by said compound of formula X and CF₃CO₂H.

400. The composition of claim 379, wherein said oxidizing agent is O₂.

401. The composition of claim 379, wherein about 1% to about 70% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

402. The composition of claim 379, wherein about 5% to about 50% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

403. The composition of claim 379, wherein about 5% to about 30% of the thiol groups present in said dendrimeric macromolecule form a disulfide bond.

404. The composition of claim 292, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

405. The composition of claim 292, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

406. The composition of claim 292, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

407. The composition of claim 292, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

408. The composition of claim 292, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

409. The composition of claim 292, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel. 410. The composition of claim 292, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

411. The composition of claim 292, wherein said nanoparticles are present in about 1 to about 40 weight percent. 412. The composition of claim 292, wherein said nanoparticles are present in about 5 to about 25 weight percent.

413. The composition of claim 292, wherein the diameter of said microparticles is less than about 50 nm.

414. The composition of claim 292, wherein the diameter of said microparticles is less than about 20 nm.

415. The composition of claim 292, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

416. The composition of claim 292, wherein said lens is transparent.

417. The composition of claim 292, wherein said lens swells less, than about 100% in an aqueous solution.

418. The composition of claim 292, further comprising a material that absorbs ultraviolet light.

419. The composition of claim 292, wherein said composition has a sterility assurance level of at least about 10^"3. 420. The composition of claim 292, wherein said composition has a sterility assurance level of at least about 10^"s.

421. A lens composition comprising nanoparticles and a hydrogel, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

422. The composition of claim 421, wherein said nanoparticles remain dispersed when placed in an aqueous solution having a pH of about 7.0.

423. The composition of claim 421, wherein said hydrogel comprises a dendrimeric macromolecule. 424. The composition of claim 421, wherein said hydrogel comprises a dendrimeric macromolecule and polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6- hydroxyhexyl methacrylate. 425. The composition of claim 421, wherein said hydrogel comprises a dendrimeric macromolecule formed by treating a dendrimeric compound of formula Ia or formula Ib with a polymerization agent selected from the group consisting of ultraviolet light, visible light, compound II, compound III, compound IV, and compound V; wherein formulae Ia, Ib, II, III, IV, and V are as defined in the specification. 426. The composition of claim 421, wherein said hydrogel comprises a dendrimeric macromolecule formed by treating a compound of formula VIII, IX, or X with an oxidizing agent sufficient to polymerize said dendrimeric compound, wherein formulae VIII, IX, and X are as defined in the specification.

427. The composition of claim 421, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

428. The composition of claim 421, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

429. The composition of claim 421, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

430. The composition of claim 421, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

431. The composition of claim 421, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

432. The composition of claim 421, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

433. The composition of claim 421, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide. 434. The composition of claim 421, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

435. The composition of claim 421, wherein said composition has a sterility assurance level of at least about 10^'3.

436. The composition of claim 421, wherein said composition has a sterility assurance level of at least about 10^~5.

437. A kit for the preparation of a lens, comprising: a polymerizable dendrimeric compound; nanoparticles; and a system for delivering said mixture to a lens bag of a patient. 438. The kit of claim 437, wherein said system is a syringe.

439. The kit of claim 437, further comprising a capulorrhexis plug

440. The kit of claim 437, further comprising a desiccant.

441. The kit of claim 437, further comprising an inert atmosphere to prevent reaction of said dendrimeric compound or said nanoparticles with atmospheric molecules. 442. The kit of claim 437, further comprising the polymerization agent.

443. The kit of claim 442, wherein said polymerization agent is compound II, compound III, compound IV, compound V, or compound VII; wherein compound π, compound HI, compound IV, compound V, and compound VII are as defined in the specification.

444. The kit of claim 442, wherein said polymerization agent is compound III or compound IV, and compound III and compound IV are as defined in the specification.

445. The kit of claim 437, wherein said dendrimeric compound is represented by formula Ia, formula Ib, or formula VI; wherein formula Ia, formula Ib, and formula VI are as defined in the specification.

446. The kit of claim 437, wherein said dendrimeric compound is represented by formula Ia or formula Ib, wherein formula Ia and formula Ib are as defined in the specification.

447. The kit of claim 437, wherein said dendrimeric compound is represented by formula VIII, formula IX, or formula X; wherein formula VIII, formula IX, and formula X are as defined in the specification.

448. The kit of claim 437, wherein said dendrimeric compound and nanoparticles are combined to form a mixture.

449. The kit of claim 437, wherein said kit has a sterility assurance level of at least about 1(T³. 450. The kit of claim 437, wherein said kit has a sterility assurance level of at least about lo-⁵.

451. A method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a non- reversible hydrogel.

452. The method of claim 451, wherein said first mixture further comprises water.

453. The method of claim 451, wherein said first mixture further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

454. The method of claim 451, wherein said polymerizable dendrimeric compound is represented by formula Ia or formula Ib, wherein formula Ia and formula Ib are as described above.

455. The method of claim 451, wherein said polymerization agent is ultraviolet light, visible light, compound II, compound III, compound IV, or compound V; wherein compound II, compound III, compound IV, and compound V are as defined in the specification. 456. The method of claim 451, wherein said polymerizable dendrimeric compound is a compound of formula VI and said polymerization agent is a compound of formula VII, wherein formula VI and formula VII are as defined in the specification.

457. The method of claim 451, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof. 458. The method of claim 451, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon-based nanoparticles.

459. The method of claim 451, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

460. The method of claim 451, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

461. The method of claim 451, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

462. The method of claim 451, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

463. The method of claim 451, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel.

464. The method of claim 451, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

465. The method of claim 451, wherein said nanoparticles are present in about 1 to about 40 weight percent in said hydrogel.

466. The method of claim 451, wherein said nanoparticles are present in about 5 to about 25 weight percent in said hydrogel.

467. The method of claim 451, wherein the diameter of said microparticles is less than about 50 nm. 468. The method of claim 451, wherein the diameter of said microparticles is less than about 20 nm.

469. The method of claim 451, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens.

470. The method of claim 451, wherein said lens is transparent. 471. The method of claim 451, wherein said lens swells less than about 100% in aqueous solution.

472. The method of claim 451, wherein said mixture further comprises a material that absorbs ultraviolet light.

473. The method of claim 451, wherein said lens forms in vivo. 474. The method of claim 451, further comprising the steps of sterilizing said nanoparticles, and admixing said microparticles with the polymerizable dendrimeric compound to form said first mixture.

475. The method of claim 474, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

476. The method of claim 474 or 475, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said nanoparticles.

477. The method of claim 474 or 475, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said nanoparticles. 478. The method of claim 451, further comprising the steps of sterilizing said hydrogel.

479. The method of claim 478, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

480. The method of claim 478 or 479, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^'3 for said hydrogel.

481. The method of claim 478 or 479, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said hydrogel. 482. The method of claim 451, further comprising the step of administering said first mixture to a lens bag of a patient.

483. The method of claim 451 or 482, wherein said first mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5.

484. The method of claim 451 or 482, wherein said first mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

485. The method of claim 451 or 482, wherein said first mixture is an aqueous buffer solution that has a pH of about 7.4.

486. The method of claim 482, wherein the step of administering the first mixture is performed using a syringe. 487. The method of claim 451, further comprising the step of administering said second mixture to a lens bag of a patient.

488. The method of claim 487, wherein the step of administering the second mixture is performed using a syringe.

489. The method of claim 451 or 487, wherein said second mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5.

490. The method of claim 451 or 487, wherein said second mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

491. The method of claim 451 or 487, wherein said second mixture is an aqueous buffer solution that has a pH of about 7.4. 492. The method of claim 451, wherein said patient is a primate, equine, feline, or canine.

493. The method of claim 451 , wherein said patient is a human.

494. The method of claim 451, wherein less than about 30% of the thiol groups present in said hydrogel form a disulfide bond.

495. The method of claim 451, wherein less than about 15% of the thiol groups present in said hydrogel form a disulfide bond.

496. The method of claim 451, wherein less than about 5% of the thiol groups present in said hydrogel form a disulfide bond. 497. The method of claim 451, wherein less than about 1% of the thiol groups present in said hydrogel form a disulfide bond.

498. A method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a reversible hydrogel.

499. The method of claim 498, wherein said mixture further comprises water.

500. The method of claim 498, wherein said mixture further comprises a polymer selected from the group consisting of a polyacrylate, siloxane, silicone, polymethylmethacrylate, styrene-ethylene-butylene-styrene block copolymer, polyvinyl alcohol, polyurethane, and a copolymer of 2-hydroxyethyl methacrylate and 6-hydroxyhexyl methacrylate.

501. The method of claim 498, wherein said polymerizable dendrimeric compound is represented by formula VIII, formula IX, or formula X; wherein formula VIII, formula IX, and formula X are as defined in the specification.

502. The method of claim 498, wherein said polymerizable dendrimeric compound is represented by formula VIII, wherein formula VIII is as defined in the specification.

503. The method of claim 498, wherein said polymerization agent is O₂.

504. The method of claim 498, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

505. The method of claim 498, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

506. The method of claim 498, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

507. The method of claim 498, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

508. The method of claim 498, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound.

509. The method of claim 498, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

510. The method of claim 498, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

511. The method of claim 498, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group. 512. The method of claim 498, wherein said nanoparticles are covalently bonded to a polymer in said hydrogel.

513. The method of claim 498, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5. 514. The method of claim 498, wherein said nanoparticles are present in about 1 to about 40 weight percent in said hydrogel.

515. The method of claim 498, wherein said nanoparticles are present in about 5 to about 25 weight percent in said hydrogel.

516. The method of claim 498, wherein the diameter of said microparticles is less than about 50 nm.

517. The method of claim 498, wherein the diameter of said microparticles is less than about 20 nm.

518. The method of claim 498, wherein said lens is an intraocular lens, accommodating intraocular lens, or endocapsular lens. 519. The method of claim 498, wherein said lens is transparent.

520. The method of claim 498, wherein said lens swells less than about 100% in aqueous solution.

521. The method of claim 498, said mixture further comprises a material that absorbs ultraviolet light. 522. The method of claim 498, wherein said lens forms in vivo.

523. The method of claim 498, further comprising the steps of sterilizing said nanoparticles, and admixing said microparticles with the polymerizable dendrimeric compound to form said first mixture.

524. The method of claim 523, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

525. The method of claim 523 or 524, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said nanoparticles.

526. The method of claim 523 or 524, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"5 for said nanoparticles.

527. The method of claim 498, further comprising the steps of sterilizing said hydrogel.

528. The method of claim 527, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration. 529. The method of claim 527 or 528, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3 for said hydrogel.

530. The method of claim 527 or 528, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^'5 for said hydrogel.

531. The method of claim 498, further comprising the step of administering said first mixture to a lens bag of a patient.

532. The method of claim 531, wherein the step of administering the first mixture is performed using a syringe.

533. The method of claim 498 or 531, wherein said first mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5.

534. The method of claim 498 or 531, wherein said first mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

535. The method of claim 498 or 531, wherein said first mixture is an aqueous buffer solution that has a pH of about 7.4. 536. The method of claim 498, further comprising the step of administering said second mixture to a lens bag of a patient.

537. The method of claim 536, wherein the step of administering the second mixture is performed using a syringe.

538. The method of claim 498 or 536, wherein said second mixture is an aqueous buffer solution that has a pH between about 5.5 and about 8.5.

539. The method of claim 498 or 536, wherein said second mixture is an aqueous buffer solution that has a pH between about 6.5 and about 7.5.

540. The method of claim 498 or 536, wherein said second mixture is an aqueous buffer solution that has a pH of about 7.4. 541. The method of claim 498, wherein said patient is a primate, equine, feline, or canine.

542. The method of claim 498, wherein said patient is a human.

543. A method for preparing a lens composition, comprising the steps of: treating a first mixture comprising a polymerizable dendrimeric compound and nanoparticles with a polymerization agent to form a second mixture that forms a hydrogel, wherein said nanoparticles are stable, and said nanoparticles remain dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

544. The method of claim 543, wherein said mixture further comprises water.

545. The method of claim 543, wherein said nanoparticles remain dispersed when placed in an aqueous solution having a pH of about 7.0. 546. The method of claim 543, wherein said hydrogel comprises a dendrimeric macromolecule.

547. The method of claim 546, wherein said dendrimeric compound is a compound of formula Ia or formula Ib, and said polymerization agent selected from the group consisting of ultraviolet light, visible light, compound II, compound III, compound IV, and compound V; wherein formulae Ia, Ib₅ π, III, IV, and V are as defined in the specification.

548. The method of claim 546, wherein said dendrimeric compound is a compound of formulae VIII, IX, or X, and said polymerization agent is an oxidizing agent, wherein formulae formulae VIII, IX, and X are as defined in the specification.

549. The method of claim 543, wherein said nanoparticles are a metal, metal oxide, metal sulfide, zeolite, protein, ceramic, silica, or a combination thereof.

550. The method of claim 543, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, silicon dioxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, silica, or carbon-based nanoparticles.

551. The method of claim 543, wherein said nanoparticles are titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, ceramic, or carbon-based nanoparticles.

552. The method of claim 543, wherein said nanoparticles are zinc oxide, aluminium oxide, diamond, zirconium dioxide, cerium dioxide, calcium oxide, or carbon-based nanoparticles.

553. The method of claim 543, wherein said nanoparticles are a metal oxide coated with an organic compound, a metal sulfoxide coated with an organic compound, or a ceramic material coated with an organic compound. 554. The method of claim 543, wherein said nanoparticles are a metal oxide coated with a layer of silica or a ceramic material coated with a layer of silica.

555. The method of claim 543, wherein said nanoparticles comprise a core coated with a layer of silica or functionalized with an organic compound, and said core comprises titanium dioxide, zinc oxide, aluminum oxide, diamond, zirconium dioxide, cerium dioxide, or calcium oxide.

556. The method of claim 543, wherein said nanoparticles have a core comprising titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

557. The method of claim 543, further comprising the step of sterilizing said nanoparticles and said polymerizable compound.

558. The method of claim 557, wherein said sterilizing is performed by treatment with ethylene oxide, hydrogen peroxide, heat, gamma irradiation, electron beam irradiation, microwave irradiation, visible light irradiation or filtration.

559. The method of claim 557 or 558, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"3.

560. The method of claim 557 or 558, wherein said sterilizing is effective to achieve a sterility assurance level of at least about 10^"s.

561. A method for preparing a titanium dioxide nanoparticle functionalized with an α- hydroxy alkanoic acid, comprising the step of: admixing a titanium dioxide nanoparticle with an α-hydroxy alkanoic acid to form a functionalized nanoparticle.

562. The method of claim 561, wherein the temperature is in the range of about 50-100 ⁰C.

563. The method of claim 561, wherein said α-hydroxy alkanoic acid is an α-hydroxy (Ci-C₆)alkanoic acid.

564. The method of claim 571, wherein said α-hydroxy alkanoic acid is lactic acid.

565. A method for preparing a titanium dioxide nanoparticle functionalized with a silyl group, comprising the step of: admixing an N-(trialkoxysilylalkyl)dialkylene triamine with a l-hydroxy-2,3- epoxyalkyl group to form a silanating agent, and admixing said silanating agent with a titanium dioxide nanoparticle.

566. The method of claim 565, wherein the temperature is in the range of about 50-100 ⁰C.

567. The method of claim 565, wherein said N-(trialkoxysilylalkyl)dialkylene triamine is N, 1 -(3-trimethoxysilylpropyl)diethylene triamine.

568. The method of claim 565, wherein said l-hydroxy-2,3-epoxyalkyl group is glycidol.

569. The method of claim 565 or 566, wherein said N-(trialkoxysilylalkyl)dialkylene triamine is N,l-(3-trimethoxysilylpropyl)diethylene triamine, and said l-hydroxy-2,3- epoxyalkyl group is glycidol.

570. A nanoparticle comprising a core coated with silica or functionalized with an organic compound, wherein said core comprises a metal, metal oxide, metal sulfide, zeolite, ceramic, diamond, carbon, protein, or a combination thereof.

571. The nanoparticle of claim 570, wherein said core comprises titanium dioxide, zinc oxide, aluminium oxide, gold, diamond, silver oxide, zirconium dioxide, cerium dioxide, calcium oxide, protein, ceramic, or carbon.

572. The nanoparticle of claim 570, wherein said core comprises titanium dioxide or ceramic.

573. The nanoparticle of claim 570, wherein said core is coated with silica. 574. The nanoparticle of claim 570, wherein said core comprises ceramic, and said core is coated with silica.

575. The nanoparticle of claim 570, wherein said core is ceramic, and said core is coated with silica.

576. The nanoparticle of claim 570, wherein said core comprises titanium dioxide, and said core is coated with silica.

577. The nanoparticle of claim 570, wherein said core comprises titanium dioxide, and said core is functionalized with lactic acid or a trimethoxysilyl group.

578. The nanoparticle of claim 570, wherein said core comprises titanium dioxide, and said core is functionalized with an α-hydroxy alkanoic acid. 579. The nanoparticle of claim 570, wherein said core comprises titanium dioxide, and said core is functionalized with lactic acid.

580. The nanoparticle of claim 570, wherein said nanoparticles have a sterility assurance level of at least about 10^"3.

581. The nanoparticle of claim 570, wherein said nanoparticles have a sterility assurance level of at least about 10^"s.

582. A stable nanoparticle that remains dispersed when placed in an aqueous solution, wherein the aqueous solution has a pH in the range of about 6.0 to about 8.0.

583. The nanoparticle of claim 582, wherein said nanoparticle remains dispersed when placed in an aqueous solution having a pH in the range of about 6.5 to about 7.5.

584. The nanoparticle of claim 582, wherein said nanoparticle remains dispersed when placed in an aqueous solution having a pH of about 7.0.