WO2009131692A1 - Substrates for delivery of physiologically active agents - Google Patents

Abstract

Disclosed are substrates that can deliver one or more physiologically active agents. The substrates can be combined with regenerated cellulose to form cellulose composites that serve as a method for delivering the physiologically active agents in vivo, in vitro, and ex vivo.

Description

SUBSTRATES FOR DELIVERY OF PHYSIOLOGICALLY ACTIVE AGENTS

FIELD

Disclosed are substrates that can deliver one or more physiologically active agents. The substrates can be combined with regenerated cellulose to form cellulose composites that serve as a method for delivering the physiologically active agents in vivo, in vitro, and ex vivo.

BACKGROUND

Entrapped materials are substances that have some restriction in their ability to freely move {e.g., dissociate, dissolve, or diffuse) in an environment. A few examples of entrapped materials are a bioactive agent encapsulated in a microcapsule, a reactive agent coated onto a substrate, an enzyme covalently attached to a bead, or a macromolecule entangled in a gel or fiber matrix. Having a wide number of uses, such as controlled release systems, structural modifiers, and sensor or reactive materials, entrapped materials and methods for their preparation are an important field of research.

Typically, entrapped materials are formulated as membranes, coatings, or capsules. Current methods for forming such materials include emulsion polymerization, interfacial polymerization, dissolution, emulsification, gelation, spray-drying, vacuum coating, and adsorption onto porous particles. Common materials used in these methods include polymers, hydrocolloids, sugars, waxes, fats, metals, and metal oxides.

For the controlled release of entrapped liquid materials, the use of membranes, coatings, capsules, etc., is well known. For example, controlled-release materials have been used in the preparation of graphic arts materials, pharmaceuticals, food, and pesticide formulations, hi agriculture, controlled-release techniques have improved the efficiency of herbicides, insecticides, fungicides, bactericides, and fertilizers. Non-agricultural uses include encapsulated dyes, inks, pharmaceuticals, flavoring agents, and fragrances. The most common forms of controlled-release materials are coated droplets or microcapsules, coated solids, including both porous and non-porous particles, and coated aggregates of solid particles, hi some instances, a water-soluble encapsulating film is desired, which releases the encapsulated material when the capsule is placed in contact with water. Other coatings are designed to release the entrapped material when the capsule is ruptured or degraded by external force. Still further coatings are porous in nature and release the entrapped material to the surrounding medium at a slow rate by diffusion through the pores.

Other materials have been formulated as emulsifiable concentrates by dissolving the materials in an organic solvent mixed with a surface-active agent or as an oily agent. In solid form, insecticides have been formulated as a wettable powder in which the insecticide is adsorbed onto finely powdered mineral matter or diatomaceous earth, as a dust or as granules.

Enzymes and proteins have become popular materials for entrapment. For example, enzyme entrapment on a solid support has been studied extensively as a simple means of protein stabilization and catalyst separation and recovery from reaction systems (Gemeiner, In Enzyme Engineering, Gemeiner, Ed., Ellis Horwood Series in Biochemistry and Biotechnology, Ellis Horwood Limited: West Sussex, England, 1992, pp 158-179; Mulder, Basic Principles of Membrane Technology, Kluwer Academic Publishers: Dordrecht, 1991). Entrapment of enzymes on solid supports can result in improved stability to pH and temperature and aid in separation of the enzyme from the reaction mixture, and also for formation of enzyme electrodes for sensor applications.

There are four principal methods available for immobilizing enzymes and other proteins: adsorption, covalent binding, entrapment, and membrane confinement. Typical materials used for these purposes include silica, polyaniline, acrylics, chitin, and cellulose (Gemeiner, In Enzyme Engineering, Gemeiner, Ed., Ellis Horwood Series in Biochemistry and Biotechnology, Ellis Horwood Limited: West Sussex, England, 1992, pp 158-179; Krajewska, Enz Microb Technol 2004, 35:126-139). Entrapment of enzymes within gels or fibers is typically used in processes involving low molecular weight substrates and products. Entrapment in calcium alginate is also used for immobilization of microbial, animal, and plant cells.

For entrapping proteins and other biomolecules, the use of cellulose, which is hydrophilic and wettable, can be desirable because it helps create a compatible environment as compared to hydrophobic materials (Tiller et al., Biotechnol Appl Biochem 1999, 30:155- 162; Sakai, JMembr Sci 1994, 96:91-130). In addition, cellulose is robust, chemically inert under physiological conditions, and non-toxic, all of which are important for protein survival and advantageous for industrial processing. One method for enzyme immobilization uses polysaccharide activation in which cellulose beads are reacted under alkali conditions with cyanogen bromide. The intermediate produced is then covalently coupled with soluble enzymes. Enzymes can also be entrapped in cellulose acetate fibers by formulation of an emulsion of the enzyme plus cellulose acetate in dichloromethane, followed by extrusion of fibers.

In other examples, materials can be entrapped by dissolving and reconstituting cellulose. However, traditional cellulose dissolution processes, including the cuprammonium and xanthate processes, are often cumbersome or expensive and require the use of unusual solvents, typically with a high ionic strength and are used under relatively harsh conditions. (Kirk-Othmer, Encyclopedia of Chemical Technology, Fourth Edition 1993, Vol. 5, p. 476-563.) Such solvents include carbon disulfide, N-methylmorpholine-N- oxide (NMMNO), mixtures of NJV-dimethylacetamide and lithium chloride (DMAC/LiCl), dimethylimidazolone/LiCl, concentrated aqueous inorganic salt solutions (e.g., ZnCl/H₂O, Ca(SCN)₂ZH₂O), concentrated mineral acids {e.g., H₂SO₄ZH₃PO₄), or molten salt hydrates (e.g., LiC10₄-3H₂0, NaSCNZKSCNZLiSCNZH₂O). These cellulose dissolution processes break the cellulose polymer backbone, resulting in regenerated products that contain an average of about 500 to about 600 glucose units per molecule rather than the native larger number of about 1500 or more glucose units per molecule. In addition, processes such as that used in rayon formation proceed via xanthate intermediates and tend to leave some residual derivatized (substituent groups bonded to) glucose residues, as in xanthate group- containing cellulose. U.S. Pat. No. 5,792,399 discloses the use of N-methylmorpholine-N-oxide

(NMMNO) solutions of cellulose to prepare regenerated cellulose that contained polyethyleneimine (PEI). That patent discloses that one should utilize a pre-treatment with the enzyme cellulase to lessen the molecular weight of the cellulose prior to dissolution. In addition, it discloses that NMMNO decomposes at the temperatures used for dissolution to provide N-methylmorpholine as a degradation product that could be steam distilled away from the cellulose solution. The presence of PEI is said to lessen the decomposition of the ΝMMΝO.

Other processes that can provide a solubilized cellulose do so by forming a substituent that is intended to remain bonded to the cellulose, such as where cellulose esters like the acetate and butyrate esters are prepared, or where a carboxymethyl, methyl, ethyl, C₂-C₃ 2-hydroxyalkyl (hydroxyethyl or hydroxypropyl), or the like group is added to the cellulose polymer. Such derivative (substituent) formation also usually leads to a lessening of the degree of cellulose polymerization so that the resulting product contains fewer glucose units per molecule than the cellulose from which it was prepared.

Against this background, many formulations of entrapped materials pose a variety of problems, such as the pollution of the environment caused by organic solvents used in the emulsions and by dust resulting from the wettable powders, and the costs associated with the removal of unwanted byproducts. Also, the use of cellulose in such compositions is generally associated with a number of drawbacks, most notably, the need for extensive chemical activation and functionalization necessary in order to attach biomolecules to the surface (Klemm et ah, Comprehensive Cellulose Chemistry, Wiley VCH: Chichester, 1998; Vol. 2.; Chesney et ah, Green Chem 2000, 2:57-62; Stδllner et al., Anal Biochem 2001, 304: 157- 165). Methods that involve cellulose solubilization can suffer from a break-down of the cellulose backbone, the requirement of exotic solvents and additional steps, and unwanted derivatization of the cellulose. Furthermore, for these formulations to have long- term residual effectiveness, an amount of entrapped material much higher than that used in normal applications can be required, and this increased amount can affect the environment or cause problems of safety.

SUMMARY

Disclosed herein are substrates that can release one or more physiologically active agents, inter alia, pharmaceuticals, flavoring ingredients, perfume and/or fragrance ingredients, and biologically active substrates. The substrates comprise biohydrolyzable links that tether the physiologically active agent to a core polymeric material that is stable during processing and storage, but which is unstable in vivo, in vitro, and ex vivo wherein the active agent is released.

In one embodiment of the disclosure, the substrates are combined with regenerated cellulosic material. The entrapped substrates can be used to deliver one or more of the disclosed physiologically active agents. In another embodiment disclosed herein, the substrates can be modified by crosslinking to better affect the entrapment of the substrate into the cellulosic material matrix.

DETAILED DESCRIPTION

The materials, compounds, compositions, articles, and methods described herein may be understood more readily by reference to the following detailed description of specific aspects of the disclosed subject matter and the Examples included therein and to the Figures. Before the present materials, compounds, compositions, articles, and methods are disclosed and described, it is to be understood that the aspects described below are not limited to specific synthetic methods or specific reagents, as such may, of course, vary. It is also to be understood that the terminology used herein is for the purpose of describing particular aspects only and, unless a particular term is specifically defined herein, is not intended to be limiting.

Also, throughout this specification, various publications are referenced. The disclosures of these publications in their entireties are hereby incorporated by reference into this application in order to more fully describe the state of the art to which the disclosed matter pertains. The references disclosed are also individually and specifically incorporated by reference herein for the material contained in them that is discussed in the sentence in which the reference is relied upon. Definitions

Throughout the description and claims of this specification the word "comprise" and other forms of the word, such as "comprising" and "comprises," means including but not limited to, and is not intended to exclude, for example, other additives, components, integers, or steps.

As used in the description and the appended claims, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a composition" includes mixtures of two or more such compositions, reference to "an ionic liquid" includes mixtures of two or more such ionic liquids, reference to "the compound" includes mixtures of two or more such compounds, and the like.

"Optional" or "optionally" means that the subsequently described event or circumstance can or cannot occur, and that the description includes instances where the event or circumstance occurs and instances where it does not.

Ranges can be expressed herein as from "about" one particular value, and/or to "about" another particular value. When such a range is expressed, another aspect includes from the one particular value and/or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent "about," it will be understood that the particular value forms another aspect. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint. It is also understood that there are a number of values disclosed herein, and that each value is also herein disclosed as "about" that particular value in addition to the value itself. For example, if the value "10" is disclosed, then "about 10" is also disclosed. It is also understood that when a value is disclosed, then "less than or equal to" the value, "greater than or equal to the value," and possible ranges between values are also disclosed, as appropriately understood by the skilled artisan. For example, if the value "10" is disclosed, then "less than or equal to 10" as well as "greater than or equal to 10" is also disclosed. It is also understood that throughout the application data are provided in a number of different formats and that this data represent endpoints and starting points and ranges for any combination of the data points. For example, if a particular data point "10" and a particular data point "15" are disclosed, it is understood that greater than, greater than or equal to, less than, less than or equal to, and equal to 10 and 15 are considered disclosed as well as between 10 and 15. It is also understood that each unit between two particular units are also disclosed. For example, if 10 and 15 are disclosed, then 11, 12, 13, and 14 are also disclosed.

Substituted and unsubstituted acyclic units comprising from 1 to 24 carbon atoms encompass 3 categories of units: linear or branched alkyl, non-limiting examples of which . include, methyl (Ci), ethyl (C₂), n-propyl (C₃), /sø-propyl (C₃), n-butyl (C₄), sec-butyl (C₄), /so-butyl (C₄), tert-butyl (C₄), and the like; substituted linear or branched alkyl, non-limiting examples of which includes, hydroxymethyl (C₁), chloromethyl (C₁), trifiuoromethyl (Ci), aminomethyl (Ci), 1-chloroethyl (C₂), 2-hydroxyethyl (C₂), 1 ,2-difluoroethyl (C₂), 3- . carboxypropyl (C₃), and the like; linear or branched alkenyl, non-limiting examples of which include, ethenyl (C₂), 3-propenyl (C₃), 1-propenyl (also 2-methylethenyl) (C₃), isopropenyl (also 2-methylethen-2-yl) (C₃), buten-4-yl (C₄), and the like; substituted linear or branched alkenyl, non-limiting examples of which include, 2-chloroethenyl (also 2- chloro vinyl) (C₂), 4-hydroxybuten-l-yl (C₄), 7-hydroxy-7-methyloct-4-en-2-yl (C₉), 7- hydroxy-7-methyloct-3,5-dien-2-yl (CQ), and the like; and linear or branched alkynyl, non- limiting examples of which include, ethynyl (C₂), prop-2-ynyl (also propargyl) (C₃), propyn-1-yl (C₃), and 2-methyl-hex-4-yn-l-yl (C₇); substituted linear or branched alkynyl, non-limiting examples of which include, 5-hydroxy-5-methylhex-3-ynyl (C₇), 6-hydroxy-6- methylhept-3-yn-2-yl (C₈), 5-hydroxy-5-ethylhept-3-ynyl (C₉), and the like. Substituted and unsubstituted cyclic units comprising from 3 to 24 carbon atoms encompass the following units: carbocyclic rings having a single substituted or unsubstituted hydrocarbon ring, non-limiting examples of which include, cyclopropyl (C₃), 2-methyl-cyclopropyl (C₃), cyclopropenyl (C₃), cyclobutyl (C₄), 2,3-dihydroxycyclobutyl (C₄), cyclobutenyl (C₄), cyclopentyl (C₅), cyclopentenyl (C₅), cyclopentadienyl (C₅), cyclohexyl (C₆), cyclohexenyl (C₆), cycloheptyl (C₇), cyclooctanyl (Cg), decalinyl (C 1₀), 2,5-dimethylcyclopentyl (C₅), 3,5-dichlorocyclohexyl (C₆), 4-hydroxycyclohexyl (C₆), and 3,3,5-trimethylcyclohex-l-yl (C₆); carbocyclic rings having two or more substituted or unsubstituted fused hydrocarbon rings, non-limiting examples of which include, octahydropentalenyl (C₈), octahydro-lH-indenyl (C₉), 3a,4,5,6,7,7a-hexahydro-3H-inden-4- yl (C9), decahydroazulenyl (Ci₀); and carbocyclic rings which are substituted or unsubstituted bicyclic hydrocarbon rings, non- limiting examples of which include, bicyclo- [2.1.1]hexanyl, bicyclo[2.2.1]heptanyl, bicyclo[3.1.1]heptanyl, l,3-dimethyl[2.2.1]heptan- 2-yl, bicyclo[2.2.2]octanyl, and bicyclo[3.3.3]undecanyl.

Substituted and unsubstituted aryl units comprising from 6 to 24 carbon atoms encompass the following units: C₆, Cio, or C_H substituted or unsubstituted aryl rings; phenyl, naphthyl, anthracenyl, phenanthryl, and the like whether substituted or • unsubstituted, non-limiting examples of which include, phenyl (C₆), naphthylen-1-yl (C ₁₀), naphthylen-2-yl (C₁₀), 4-fluorophenyl (C₆), 2-hydroxyphenyl (C₆), 3-methylphenyl (C₆), 2- amino-4-fluorophenyl (C₆), 2-(NJV-diethylamino)phenyl (C₆), 2-cyanophenyl (C₆), 2,6-di- tert-butylphenyl (C₆), 3-methoxyphenyl (C₆), 8-hydroxynaphthylen-2-yl (C₁₀), 4,5- dimethoxynaphthylen-1-yl (Ci₀), and 6-cyano-naphthylen-l-yl (Cio); C₆, C₁₀, or C₁₄ aryl rings fused with 1 or 2 saturated rings non-limiting examples of which include, bicyclo[4.2.0]octa-l,3,5-trienyl (C₈), and indanyl (C₉).

Substituted and unsubstituted heterocyclic or heteroaryl units comprising from 1 to 24 carbon atoms encompasses the following units all of which contain at least one heteroatom in at least one ring chosen from nitrogen (N), oxygen (O), sulfur (S), phosphorous (P) or mixtures of N, O, S, and P: heterocyclic units having a single ring containing one or more heteroatoms chosen from nitrogen (N), oxygen (O), or sulfur (S), or mixtures of N, O, and S, non-limiting examples of which include, diazirinyl (C₁), aziridinyl (C₂), urazolyl (C₂), azetidinyl (C₃), pyrazolidinyl (C₃), imidazolidinyl (C₃), oxazolidinyl (C₃), isoxazolinyl (C₃), isoxazolyl (C₃), thiazolidinyl (C₃), isothiazolyl (C₃), isothiazolinyl (C₃), oxathiazolidinonyl (C₃), oxazolidinonyl (C₃), hydantoinyl (C₃), tetrahydrofuranyl (C₄), pyrrolidinyl (C₄), morpholinyl (C₄), piperazinyl (C₄), piperidinyl (C₄), dihydropyranyl (C₅), tetrahydropyranyl (C₅), piperidin-2-onyl (valerolactam) (C₅), 2,3,4,5-tetrahydro-lH- azepinyl (C₆), 2,3-dihydro-lH-indole (C₈), and 1,2,3,4-tetrahydro-quinoline (C₉); heterocyclic units having 2 or more rings one of which is a heterocyclic ring, non-limiting examples of which include hexahydro-l//-pyrrolizinyl (C₇), 3a,4,5,6,7,7a-hexahydro-lH- benzo[d]imidazolyl (C₇), 3a,4,5,6,7,7a-hexahydro-lH-indolyl (C₈), 1,2,3,4- tetrahydroquinolinyl (C₉), and decahydro-lH-cycloocta[b]pyrrolyl (C₁₀); heteroaryl rings containing a single ring, non-limiting examples of which include, 1,2,3,4-tetrazolyl (C₁), [l,2,3]triazolyl (C₂), [l,2,4]triazolyl (C₂), triazinyl (C₃), thiazolyl (C₃), lH-imidazolyl (C₃), oxazolyl (C₃), furanyl (C₄), thiopheneyl (C₄), pyrimidinyl (C₄), 2-phenylpyrimidinyl (C₄), pyridinyl (C₅), 3-methylpyridinyl (C₅), and 4-dimethylaminopyridinyl (C₅); heteroaryl rings containing 2 or more fused rings one of which is a heteroaryl ring, non-limiting examples of which include: 7H-purinyl (C₅), 9H-purinyl (C₅), 6-amino-9H-purinyl (C₅), 5H-pyrrolo[3,2- cT]pyrimidinyl (C₆), 7H-pyrrolo[2,3-(i]pyrimidinyl (C₆), pyrido[2,3-c?]pyrimidinyl (C₇), 2- phenylbenzo[d]thiazolyl (C₇), lH-indolyl (C₈), 4,5,6,7-tetrahydro-l-H-indolyl (C₈), quinoxalinyl (C₈), 5-methylquinoxalinyl (Cg), quinazolinyl (C₈), quinolinyl (C₉), 8-hydroxy- quinolinyl (C₉), and isoquinolinyl (C₉).

The term "arylalkylene" is used throughout the specification to refer to substituted or unsubstituted C₆, C ₁₀, or Cj₄ aryl rings tethered to another unit through a substituted or unsubstituted C₁-Cj₂ alkylene unit. These units can be referred to by indicating the number of carbons contained in the alkylene unit followed by the number of carbon atoms in the aryl unit, or by their chemical name. A non-limiting example of tethered cyclic hydrocarbyl units includes a substituted or unsubstituted benzyl. A substituted or unsubstituted benzyl unit contains a tether containing one carbon atom (methylene) and a substituted or unsubstituted aryl ring containing six carbon atoms, or a C₁-(C₆) unit, having the formula:

wherein R^a is optionally one or more independently chosen substitutions for hydrogen. Further examples include other aryl units, inter aha, (2-hydroxyphenyl)hexyl C₆-(C₆); naphthalen-2-ylmethyl Ci-(C₁₀), 4-fluorobenzyl C₁-(C₆), 2-(3-hydroxy- phenyl)ethyl C₂-(C₆), as well as substituted and unsubstituted C₃-Ci_O alkylenecarbocyclic units, for example, cyclopropylmethyl Cj-(C₃), cyclopentylethyl C₂-(C₅), cyclohexylmethyl Ci-(C₆).

The terms "heteroarylalkylene" and "heterocyclicalkylene" are used throughout the specification to refer to substituted or unsubstituted heteroaryl and heterocyclic rings as defined herein above containing from 1 to 24 carbon atoms that are tethered to another unit through a substituted or unsubstituted Ci-Ci₂ alkylene unit. These units can be referred to by indicating the number of carbons contained in the alkylene unit followed by the number of carbon atoms in the heteroaryl and heterocyclic unit, or by their chemical name. A non- limiting example includes substituted and unsubstituted Ci-Ci₀ alkylene-heteroaryl units, for example a 2-picolyl Ci-(C₆) unit having the formula:

wherein R^a is the same as defined above. In addition, Cj-Ci₂ tethered cyclic hydrocarbyl units include Cj-Cio alkyleneheterocyclic units and alkylene-heteroaryl units, non-limiting examples of which include, aziridinylmethyl Cj-(C₂) and oxazol-2-ylmethyl Cr(C₃). The term "substituted" is used throughout the specification. The term "substituted" is applied to the units described herein as "substituted unit or moiety is a hydrocarbyl unit or moiety, whether acyclic or cyclic, which has one or more hydrogen atoms replaced by a substituent or several substituents as defined herein below." The units, when substituting for hydrogen atoms are capable of replacing one hydrogen atom, two hydrogen atoms, or three hydrogen atoms of a hydrocarbyl moiety at a time, hi addition, these substituents can replace two hydrogen atoms on two adjacent carbons to form said substituent, new moiety, or unit. For example, a substituted unit that requires a single hydrogen atom replacement includes halogen, hydroxyl, and the like. A two hydrogen atom replacement includes carbonyl, oximino, and the like. A two hydrogen atom replacement from adjacent carbon atoms includes epoxy, and the like. A three hydrogen replacement includes cyano, and the like. The term substituted is used throughout the present specification to indicate that a hydrocarbyl moiety, inter alia, aromatic ring, alkyl chain; can have one or more of the hydrogen atoms replaced by a substituent. When a moiety is described as "substituted" any number of the hydrogen atoms may be replaced. For example, 4-hydroxyphenyl is a "substituted aromatic carbocyclic ring (aryl ring)", (N,N-dimethyl-5-amino)octanyl is a " substituted C₈ linear alkyl unit, 3-guanidinopropyl is a "substituted C₃ linear alkyl unit," and 2-carboxypyridinyl is a "substituted heteroaryl unit."

The following are non-limiting examples of units which can substitute for hydrogen atoms on a carbocyclic, aryl, heterocyclic, or heteroaryl unit: i) Ci-C₄ linear or branched alkyl; for example, methyl (Ci), ethyl (C₂), n-propyl

(C₃), wo-propyl (C₃), n-butyl (C₄), wø-butyl (C₄), sec-butyl (C₄), and tert- butyl (C₄); ii) -OR¹²; for example, -OH, -OCH₃, -OCH₂CH₃, -OCH₂CH₂CH₃; iii) -C(O)R¹²; for example, -COCH₃, -COCH₂CH₃, -COCH₂CH₂CH₃; iv) -C(O)OR¹²; for example, -CO₂CH₃, -CO₂CH₂CH₃,

CO₂CH₂CH₂CH₃; v) -C(O)N(R¹²)₂; for example, -CONH₂, -CONHCH₃, -CON(CH₃)₂; vi) -N(R¹²)₂; for example, -NH₂, -NHCH₃, -N(CH₃)₂, -NH(CH₂CH₃); vii) halogen: -F, -Cl, -Br, and -I; viii) -CH_mX_n; wherein X is halogen, m is from 0 to 2, m + n =3; for example, -

CH₂F, -CHF₂, -CF₃, -CCl₃, or -CBr₃; and ix) -SO₂R¹²; for example, -SO₂H; -SO₂CH₃; -SO₂C₆H₅ wherein each R¹² is independently hydrogen, substituted or unsubstituted Ci-C₄ linear, branched, or cyclic alkyl; or two R¹² units can be taken together to form a ring comprising 3-7 atoms. Substituents suitable for replacement of a hydrogen atom are further defined herein below. Reference will now be made in detail to specific aspects of the disclosed materials, compounds, compositions, articles, and methods, examples of which are illustrated in the accompanying Examples and Figures.

The disclosed substrates can be entrapped a regenerated cellulose matrix. Once entrapped, or prior thereto, the substrates can be further modified by crosslinking with a crosslinking agent as disclosed herein. The substrates can deliver a single physiological agent, a mixture of physiological agents, or the substrates can be formulated to deliver one or more physiological agents with an excipient, biologically compatible absorption promoting agent, or other ingredient that modulates or modifies the rate of biological uptake or the rate at which the physiologically active agent is released. SUBSTRATES

The disclosed active substrates can have the formula:

O

ϋ)

_L,- [ZA]₅

R-N

[ZA]₅. iii)

R R > ——- n rO» ——- T T L i1'——- T[ZVA A i]_S ' .-, OT iv)

R-S-I^-[ZA]₈. wherein R is an anchoring unit chosen from: i) hydrogen; ii) C₁-C₁₂ linear, branched, or cyclic alkyl; iii) C₆ or C₁₀ aryl; and iv) C₇-C₁₂ alkylenearyl; each L is a linking unit independently chosen from: i) -(CR^laR^lb)_w-; and ii) -{CR^2aR^2b)_x[X(CR^3aR^3b)y]_zX-; the index w is from 1 to 50, the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20; R^la and R^lb are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; R^2a, R^2b, R^3a, and R^3b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; iii) -(CR^5aR^5b)_jOH; and iv) -[(CR^6aR^6b)_kNH₂; R^5a, R*, R^6a, and R^6b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; the indices j and k are each independently from 2 to 20; each X is independently chosen from i) -O-; ii) -NR⁷-; iϋ) -S-; iv) -C(O)-; v) -NHC(O)-; vi) -C(O)NH-; vii) -OC(O)-; and viii) -C(O)O-;

R⁷ is -[(CR^8aR^8b)_mNH]_n(CR^9aR^9b)_pNH₂; R^8a, R^8b, R^9a, and R^9b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; the index m is from 2 to 20; the index n is from O to 6; the index p is from 2 to 20; each Z unit is independently a biohydrolyzable linking groups; each A unit is independently a precursor of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released; and the index s is 1 or 2. R units

R is an anchoring unit that provides a means for attaching the active functions groups to a central core. In addition, the R unit provides an anchoring point for attachment of the active substrates to regenerated cellulosic material.

A first category of R units relates to C₁-Ci₂ linear, branched, or cyclic alkyl moieties. One embodiment relates to lower alkyl C₁-C₄ linear alkyl R units that provide active substrates having the formulae:

Another embodiment relates to C₃-C₄ branched alkyl R units that provide active substrates having the formulae:

A further embodiment of this category includes R units chosen from n-pentyl, n- hexyl, n-heptyl, n-octyl, n-nonyl, n-decyl, n-undecyl, and n-dodecyl. A yet further embodiment includes R units chosen from cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and cycloheptyl.

Another category of R units relates to C₆ or Cio aryl R units that provide active substrates having the formulae:

A yet further category of R units relates to C₇-C₁₂ alkylenearyl R units that provide active substrates having the formulae:

A still further category of R units relates to R units that are hydrogen that provide active substrates having the formulae:

L¹, L², and L³ Units

L¹, L², and L³ units are linking units that serve to link the ZA unit to the R unit- comprising core. Each L¹, L², and L³ unit is independently chosen from: i) -<CR^laR^lb)_w-; and ii) -(CR^2aR^2b)_x[X(CR^3aR^3b)y]_zX-; the index w is from 1 to 50. In one embodiment the index w is from 2 to 12. In another embodiment the index w is from 2 to 6. In a yet further embodiment the index w is from 2 to 4. However, any value of the index w is possible, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.

The index x is from 0 to 50. One particular embodiment comprises L¹, L², and L³ units wherein the index x is equal to 1 , thereby affording a methylene unit. In another embodiment the index x is from 2 to 6. In a yet further embodiment the index x is from 2 to 4. However, any value of the index x is possible, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12.

The index y is from 2 to 12. For ethyleneoxy-comprising linking units the index y is equal to 2. For 1,2-propyleneoxy-comprising linking units the index y is equal to 2. For 1,3-propyleneoxy-comprising linking units the index y is equal to 3. For 1,4-butyleneoxy- comprising linking units the index y is equal to 4. For ethyleneimine (polyethyleneimines) comprising linking units the index y is equal to 2. In another embodiment the index y is from 2 to 6. In a yet further embodiment the index y is from 2 to 4. However, any value of the index y is possible, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. The index z is from 1 to 40. When each X is equal to oxygen, the index z indicates the number of alkyleneoxy units present in the linking group. In another embodiment the index z is from 2 to 6. In a yet further embodiment the index z is from 2 to 4. However, any value of the index z is possible, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, and 12. R^la and R^lb are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl.

In one embodiment, R^la and R^lb are both hydrogen thereby affording an alkylene linker comprising methylene units. In another embodiment, each R^la is hydrogen and alternating R^lb units are hydrogen with the other alternating unit comprising methyl, thereby affording a polyalkylene linker having, for example, the formula:

However, R^Ib units can be randomly hydrogen and C₁-C₂ alkyl thereby providing linkers having, for example, the formulae: i)

ϋ)

iii)

R^2a, R^2b, R^3a, and R^3b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; iii) -(CR⁵³R⁵^_jOH; and iv) -[(CR^6aR^6b)_kNH₂; R^5a, R^5b, R^6a, and R^6b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; the indices j and k are each independently from 2 to 20. Each X is independently chosen from i) -O-; ii) -NR⁷-; ϋi) -S-; iv) -C(O)-; v) -NHC(O)-; vi) -C(O)NH-; vii) -OC(O)-; and viii) -C(O)O-;

R⁷ is a ZA unit, a second bond to a ZA unit which serves to act together with the other bond to form a double bond, hydrogen, Ci-C₄ alkyl, or a unit having the formula - [(CR^8aR^8b)_mNH]_n(CR^9aR^9b)_pNH₂;

R^8a, R^8b, R^9a, and R^9b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; the index m is from 2 to 20; the index n is from 0 to 6; the index p is from 2 to 20.

Linking units comprising -(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX- units can be conveniently prepared by the polymerization of alkyleneoxy and alkyleneimine units or by mixtures thereof. In one embodiment, as described herein below, each X unit is oxygen thereby affording units having the general formula: -(CR^2aR^2b)_x[O(CR^3aR^3b)_y]_zO-.

In another embodiment, as described herein below, each X unit is NH, or NR⁷ thereby affording units, for example, having the general formula:

-(CR^2aR^2b)_x[NH(CR^3aR^3b)_y]_zNH-; -(CR^2aR^2b)_x[NR⁷(CR^3aR^3b)_y]_z NR⁷-; or

-(CR^2aR^2b)_x[NR⁷(CR^3aR^3b)_y]_z N=.

Each L , L , and L can be selected independently from one another, not only in the selection of moiety, inter alia, ethyleneoxy, but the number and type of substituents or units contained within the moiety. For example, linking units derived from the polymerization of starting materials such as ethylene oxide or ethyleneimine can have different lengths that vary from L¹ to L² to L³ depend upon many factors, inter alia, stoichiometry, control of polymerization, and the like. One non-limiting example includes linking units comprising alkyleneoxy moieties. One method of describing and/or representing the fact the three linking units can each have varying lengths is to use, for example, the formula: -[O(CH₂CH₂)]_Z- and recite that the value of the index z is from 2 to 5. This convention means the total number of ethyleneoxy units in the three linking units of a single molecule can total from 6 to 15. Or stated in another way, over all the range of molecules present in this embodiment, the average value of the index z is about 3.5. The first category of L unit relates to linking groups having the formula:

-(CR^laR^Ib)_w- wherein R^la and R^lb are each independently chosen from hydrogen and C₁-C₂ alkyl. The index w is from 1 to 50.

A first embodiment of this category of L¹, L², and L³ units relates to L¹, L², and L³ independently chosen from alkylene units having the formula:

-(CH₂)_W- wherein R^la and R^lb are each hydrogen; and the index w is from 2 to 20. Non- limiting examples of this category include: i) -CH₂-; ϋ) -CH₂CH₂-; iii) -CH₂CH₂CH₂-; iv) -CH₂CH₂CH₂CH₂-; v) -CH₂CH₂CH₂CH₂CH₂-; vi) -CH₂CH₂CH₂CH₂CH₂CH₂-; vii) -CH₂CH₂CH₂CH₂CH₂CH₂CH₂-; viii) -CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂-; ix) -CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂-; and x) -CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂CH₂-.

A second embodiment of this category of L¹, L², and L³ each have the formula:

-[CH₂CH(CH₃)]w- or -[CH(CH₃)CH₂]_W- wherein R^la and R^lb are each hydrogen or methyl; and the index w is from 2 to 20. Non- limiting examples of this category include: i) -CH₂CH(CH₃)-; ii) -CH(CH₃)CH₂-; iii) -CH(CH₃)CH₂CH₂CH(CH₃)-; iv) -CH₂CH(CH₃)CH₂CH(CH₃)-; Y) -CH(CHJ)CH₂CH(CH₃)CH₂-; vi) -CH₂CH(CH₃)CH(CH₃)CH₂-; vii) -CH(CH₃)CH₂CH₂CH(CH₃)CH₂CH(CH₃)-; viii) -CH₂CH(CH₃)CH₂CH(CH₃)CH₂CH(CH₃)-; ix) -CH(CH₃)CH₂CH(CH₃)CH₂CH₂CH(CH₃)-; x) -CH₂CH(CH₃)CH(CH₃)CH₂CH₂CH(CH₃)-; xi) -CH(CH₃)CH₂CH₂CH(CH₃)CH(CH₃)CH₂-; xii) -CH₂CH(CH₃)CH₂CH(CH₃)CH(CH₃)CH₂-; xiii) -CH(CH₃)CH₂CH(CH₃)CH₂CH(CH₃)CH₂-; and xiv) -CH₂CH(CH₃)CH(CH₃)CH₂CH(CH₃)CH₂-. A further category relates to L¹, L², and L³ relates to L¹, L², and L³ each independently having the formula:

-(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX- wherein R^2a, R^2b, R^3a, and R^3b are each hydrogen; X is oxygen; the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 40. A first embodiment of this category relates to polyalkyleneoxy units having the formula: -(CH₂CH₂)[O(CH₂CH₂)I₂O- wherein the index z is from 2 to 12. Non-limiting examples of this embodiment L¹, L², and L³ units independently chosen from: i) -(CH₂CH₂)[O(CH₂CH₂)]O-; ii) -(CH₂CH₂)[O(CH₂CH₂)I₂O-; ii) -(CH₂CH₂)[O(CH₂CH₂)]₃O-; iii) -(CH₂CH₂)[O(CH₂CH₂)]₄O-; iv) -(CH₂CH₂)[O(CH₂CH₂)I₅O-; v) -(CH₂CH₂)[O(CH₂CH₂)I₆O-; vi) -(CH₂CH₂)[O(CH₂CH₂)I₇O-; vii) -(CH₂CH₂)[O(CH₂CH₂)]₈O-; and viii) -(CH₂CH₂)[O(CH₂CH₂)I₉O-.

A second embodiment of this category relates to polyalkyleneoxy units having the formula:

-(CH₂)_X[O(CH₂CH(CH₃))]_ZO- or -(CH₂)_X[O(CH(CH₃)CH₂)]_ZO- wherein the index x is from 1 to 6, and the index z is from 2 to 12. Non-limiting examples of this embodiment include L¹, L², and L³ units independently chosen from: i) -(CH₂)[O(CH₂CH(CH₃))]O-; ii) -(CH₂)[O(CH₂CH(CH₃))]₂O-; iii) -(CH₂)[O(CH₂CH(CH₃))]₃O-; iv) -(CH₂)[O(CH₂CH(CH₃))]₄O-; v) -(CH₂)[O(CH₂CH(CH₃))]₅O-; vi) -(CH₂)₂[O(CH₂CH(CH₃))]₂O-; vii) -(CH₂)₂[O(CH2CH(CH₃))]₃O-; viii) -(CH₂)₂[O(CH₂CH(CH₃))]₄O-; ix) -(CH₂)₂[O(CH₂CH(CH₃))]₅O-; x) -(CH₂)₂[O(CH₂CH(CH₃))]₆O-; xi) -(CH₂)₂[O(CH(CH₃)CH₂)]O-; xii) -(CH₂)₂[O(CH(CH₃)CH₂)]₂O-; xiii) -(CH₂)₂[O(CH(CH₃)CH₂)]₃O-; xiv) -(CH₂)₂[O(CH(CH₃)CH₂)]₄O-;

XV) -(CH₂)₂[O(CH(CH₃)CH₂)]₅O-; xvi) -(CH₂)₂[O(CH₂CH(CH₃))]₂O-; xvii) -(CH₂)₂[O(CH₂CH(CH₃))]₃O-; xviii) -(CH₂)₂[O(CH₂CH(CH₃))]₄O-; xix) -(CH₂)₂[O(CH₂CH(CH₃))]₅O-; and

XX) -(CH₂)₂[O(CH₂CH(CH₃))]₆O-. Another category of L¹, L², and L³ relates to L¹, L², and L³ each independently having the formula:

-(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX- wherein R^2a, R^2b, R^3a, and R^3b are each hydrogen; X is NH; the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 40. A first embodiment of this category relates to polyalkylene imine units having the formula:

-(CH₂)_X[NH(CH₂CH₂)]₂-; wherein the index x is from 1 to 6; and the index z is from 1 to 6.

A still further category of L¹, L², and L³ relates to L¹, L², and L³ each independently having the formula:

-(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX- wherein R^2a, R^2b, R^3a, and R^3b are each hydrogen; X is NR⁷; R⁷ is hydrogen or has the formula:

^• • -[CH₂CH₂NH]_nCH₂CH₂NH₂; wherein the index n is from 0 to 6; the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 40

. A first embodiment of this category relates to polyalkylene imine units having the formula:

-(CH₂)_x[N{[CH₂CH₂NH]_nCH₂CH₂NH₂}(CH₂CH₂)]_z-; wherein the index n is form 0 to 6; the index x is from I to 6; and the index z is from 1 to 6. A non-limiting example of this category is a polyalkylene imine having the formula:

A yet further category of L¹, L², and L³ relates to L¹, L², and L³ each independently having the formula: -(CR^2aR^2b)_x[X(CR^3aR^3b)_y]₂X- wherein R^2a, R^2b, R^3a, and R^3b are each hydrogen or methyl; each X is independently O or NH; the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20.

A first embodiment of this category relates to substrates wherein the L¹, L², and L³ and core unit comprising R units can be conveniently formed from a JEFF AMINE™, for example, JEFF AMINE™ T-403. L¹, L², and L³ units of this embodiment have the formula:

-(CH₂)_X[OCH₂CH(CH₃)]_ZNH- wherein the index x is 1 or 2; and the index z is from 1 to 5. Non-limiting examples of L¹, L², and L³ units according to this embodiment include L¹, L², and L³ units independently chosen from: i) -(CH₂)[OCH₂CH(CH_S)]NH-; ii) -(CH₂)[OCH₂CH(CH₃)J₂NH-; iii) -(CH₂)[OCH₂CH(CH₃)I₃NH-; iv) -(CH₂)[OCH₂CH(CH₃)]₄NH-; v) -(CH₂)[OCH₂CH(CH₃)I₅NH-; vi) -(CH₂)₂[OCH₂CH(CH₃)]NH-; vii) -(CH_Z)₂[OCH₂CH(CH₃)I₂NH-; viii) -(CH₂)₂[OCH₂CH(CH₃)]₃NH-; ix) -(CH₂)₂[OCH₂CH(CH₃)]₄NH-; and x) -(CH₂MOCH₂CH(CH₃)J₅NH-.

For this embodiment the L¹, L², and L³ units can each have different values of the index z. For example, substrates made- from JEFF AMINE™ T-403 will have the sum of the three linking group z indices, z¹, z², and z³ have the value from about 5 to about 6. As such, the substrate can comprise any of the following combinations of linking units on a substrate molecule: a) one unit having the formula -(CH₂)[OCH₂CH(CH₃)]NH-; and b) two units having the formula -(CH₂)[OCH₂CH(CH₃)J₂NH-; or a) two units having the formula -(CH₂)[OCH₂CH(CH₃)JNH-; and b) one unit having the formula -(CH₂)[OCH₂CH(CH₃)J₃NH-; or a) one unit having the formula -(CH₂)[OCH₂CH(CH₃)]NH-; b) one unit having the formula -(CH₂)[OCH₂CH(CH₃)J₂NH-; and c) one unit having the formula -(CH₂)[OCH₂CH(CH₃)J₃NH-; or a) two units having the formula -(CH₂)[OCH₂CH(CH₃)JNH-; and b) one unit having the formula -(CH₂)[OCH₂CH(CH₃)J₄NH-; or a) three units having the formula -(CH₂)[OCH₂CH(CH₃)J₃NH-. A yet further embodiment of L¹, L², and L³ relates to L¹, L², and L³ each independently having the formula: -(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX- wherein R^2a, R^2b, R^3a, and R^3b are each hydrogen or methyl; each X is independently O or NH; the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20; and the sum of the indices x + z is from 50 to 100. For this embodiment the L¹, L², and L³ units can each have different values of the index z provided the sum of the indices x + z L¹, L², and L³ total from 50 to 100. For example, substrates made from JEFF AMINE™ T500 will have the sum of the three linking group z indices, z¹, z², and z³ have the value from about 50 to about 100. For example, the index z¹ can be 25, the index z² can be 28, and the index z³ can be 32 wherein the total of the index z is 85. ZA Units

Each Z unit is independently a biohydrolyzable linking group. Z units can be present, or in the case wherein A units form a biohydrolyzable link directly with an L¹, L², or L³ unit, Z units can be absent. Each A unit is independently a precursor of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released. The index s is 1 or 2.

"Biohydrolyzable" as used herein means a moiety or unit that can be hydrolyzed in vivo. For example, an ester linking unit is a moiety that can be hydrolyzed to an acid and an alcohol. The following examples will serve to further illustrate the meaning of the term biohydrolyzable.

Non-limiting examples of biobydrolyzable Z units linked to A units include: i) -(CR^10aR^10b)_qC(O)-A; ii) -C(O)(CR^10aR^10b)_qC(O)-A; iii) -(CR^10aR^10b)_qC(O)O-A; iv) -OC(O)(CR^10aR^10b)_qC(O)O-A; v) -(CR^1OaR^1Ob)_qNH-A; vi) -(CR^IOaR^1Ob)_qN=A; vii) -NH(CR^10aR^10b)_qC(O)-A; viii) -(CR^10aR^10b)_qC(O)NH-A; ix) -NHOC(O)(CR^10aR^10b)_qC(O)O-A; x)

Xi)

xii)

xiii)

R^1Oa and R'^Ob are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; and iii) C1-C2-OH; and the index q is from O to 10.

As such, A units comprise a moiety which is capable of forming a biohydrolyzable unit when taken together with a Z unit. For example, an A unit -OH combines with a Z unit -CO₂H to form an ester: Z-C(O)O-A. A first category of ZA units relates to acetals having the formula:

wherein R^1Oa and R^1Ob are each independently chosen from hydrogen or C₁-C₂ alkyl; and the index q is from O to 10. A units are further defined herein. A first embodiment of this category relates to ZA units having the formula:

ZA units of this embodiment are biohydrolyzed to release a physiologically active compound having the formula A-CHO according to the following scheme:

Λ + A-CHO

One non- limiting example of a physiologically active compound released by a ZA unit of this embodiment is the release of vanillin according to the scheme:

A non-limiting example of one category of substrate that comprises a ZA unit according to this embodiment has the formula:

wherein R is the same as defined herein above, R^2a, R^2b, R^3a and R^3b are each independently chosen from hydrogen and C₁-C₂ alkyl; R^1Oa and R^1Ob are each independently chosen from hydrogen and C₁-C₂ alkyl; X is O, NH, or N; the index x is from 1 to 2, the index y is from 2 to 4; the index z is from 5 to 6 and the indices z¹ + z² + z³ = z; the index q is from O to 10; the index s is 1 or 2. A non-limiting example of a compound according to this embodiment is the compound 8-ethyl-5,12,16,19-tetraamethyl-N²,N²,N²²,N²²-tetrakis(2-phenyl- l,3- dioxolan-4-yl)methyl- 1 ,2- {3,6,9-trimethyl-l -(2-phenyl- 1 ,3-dioxolan-4-yl)-2-[(2-phenyl- 1 ,3- dioxolan-4-yl)methyl]-5,8, 11 ,-trioxa-2-azadodecan-12-yl} -4,7,10, 14, 17,20- hexaoxatricosane-2,22-diamine having the formula:

that is capable of releasing benzaldehyde. The above compound can be prepared by reacting JEFF AMINE™ T-403 with 6 equivalents of oxirari-2-ylmethanol, followed by reaction of the hexadiol with benzaldehyde dimethyiacetal as described herein below in Example 1.

Another category of ZA units relates to biohydrolyzable acetals wherein the vicinal hydroxyl units are a part of the A unit, for example, acetals having the formula:

wherein R^1Oa and R^1Ob are each independently chosen from hydrogen or Ci-C₂ alkyl; and the index q is from 0 to 10. A first embodiment of this category relates to ZA units having the formula:

ZA units of this embodiment are biohydrolyzed to release a physiologically active compound wherein the released active comprises a pair of vicinal hydroxyl units or two hydroxyl units positioned such that a cyclic acetal can be formed. A non-limiting example of this embodiment includes the delivery of a saccharide according to the scheme:

A non-limiting example of a compound according to this embodiment is the compound 2,2'-(3E,26E)-15-ethyl-5,8,l l,19,22,25-hexamethyl-15-((Z)-4,7,10-trimethyl- 14-(5,7,8-trihydroxyhexahydro-4H-benzo[d][l,3]dioxin-2-yl-2,5,8-trioxa-l l-azatetradec- 11 -enyl)-7, 10, 13, 17,20,23 -hexaoxa-^ό-diazanonacosa-S^β-diene- 1 ,29- diyl)bis(hexahydro-4H-benzo[d] [ 1 ,3]dioxine-6,7,8-triol.

ZA units can be prepared and linked to the core molecule by any method chosen by the formulator. One method for attaching ZA units of this embodiment to an amino end group of a polyalkyleneoxy amine chain is outlined herein below: Step (a)

Step (b)

A further category of ZA units relates to biohydrolyzable orthoesters having the formula:

wherein each R³⁰ is independently chosen from: i) C₁-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂O aryl; v) substituted or unsubstituted C₇-C_2O alkylenearyl; vi) substituted or unsubstituted C₁-C_2O heterocyclic; and vii) substituted or unsubstituted C₁-C₂₀ heteroaryl; wherein R is the same as defined herein above.

wherein R^1Oa and R^1Ob are each independently chosen from hydrogen or C₁-C₂ alkyl; and the index q is from O to 10. A first embodiment of this category relates to ZA units having, for example, the formula:

ZA units of this embodiment are biohydrolyzed to release a physiologically active compound having the formula A-OH according to the following scheme:

One non-limiting example of a physiologically active compound released by a ZA unit of this embodiment is the release of geraniol according to the scheme:

A yet further category of ZA units relates to biohydrolyzable amides having the 10 formula -NH(CR^10aR^10b)_qC(O)-A wherein R^1Oa and R^1Ob are each independently chosen from hydrogen or Ci-C₂ alkyl; and the index q is from O to 10. A first embodiment of this category relates to ZA units having, for example, the formula:

wherein the Z unit is either absent in the case where the amide nitrogen is a part of the L¹, i 5 L², or L³ units or a part of the Z unit. Substrates according to this embodiment release the physiologically active agent according to the following reaction. H

H

-S N -$ N^ + A-CO₂H

/^~A

O

A non- limiting example of a compound according to this embodiment is the compound N,N'-(12- { 13-[2-(2,6-dichlorophenylamino)phenyl]-4,7, 10-trimethyl- 12-oxo-2,5,8-trioxa- 11 -azatridecyl} -8-ethyl-5 , 12, 16, 19-tetramethyl-4,7, 10, 14, 17,20-hexaoxatricosane-2,22- diyl)bis{2-[2-(2,6-dichlorophenylamino)phenyl]acetamide}

A-Units

A unit is independently a precursor of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released. In one embodiment, the disclosed substrates are capable of releasing a protein, nucleic acid, antibacterial, antiviral, cardiovascular therapeutic, anti-cancer therapeutic, CNS therapeutic, hypoglycemic agent, fertility/contraception or woman's health agent, infectious disease therapeutic, pulmonary disease therapeutic, or neutralizing agent. In another embodiment, the substrates are capable of releasing an aesthetic agent, inter alia, a sweetener, a flavor, or a fragrance raw material and/or a mixture thereof. In a yet further embodiment, the disclosed substrates are capable of releasing a microbial cell, herbicide, an insecticide, a fungicide, a microbial cell, a repellent for an animal or insect, a plant growth regulator, a fertilizer, a flavor or odor composition, a catalyst, a photoactive agent, an indicator, a dye, an UV adsorbent, or a mixture thereof. In a still further embodiment, the disclosed substrates are capable of releasing a biomolecule, inter alia, a peptide, protein, enzyme, antibody, nucleic acid, aptamer, or ribozyme. In addition, the substrates disclosed herein are capable of releasing a wetting agent, inter alia, oleyl alcohol or cetyl alcohol.

For example, vanillin represented as an physiologically active agent has the formula A-CHO, wherein the A component of this physiologically active agent has the formula:

In the case wherein a physiologically active agent has a plurality of moieties that can form a biohydrolyzable bond with a Z unit, the formulator can chose one unit over another or use a combination of both units.

In one embodiment, the A units comprise a physiologically active compound having the formula:

wherein A is chosen from: i) C₁-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C_2O aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted Ci-C₂₀ heterocyclic; and vii) substituted or unsubstituted C₁-C₂₀ heteroaryl.

In a further embodiment, the A units comprise a physiologically active compound having the formula:

wherein A is chosen from: i) C₁-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C_O-C_2O aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted C]-C₂O heterocyclic; and vii) substituted or unsubstituted C i -C₂o heteroaryl. In a still further embodiment, the A units comprise a physiologically active compound having the formula:

HO-A wherein A is chosen from: i) C₁-C_2O substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C_2O substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C_2O aryl; v) substituted or unsubstituted C₇-C_2O alkylenearyl; vi) substituted or unsubstituted Cj-C_2O heterocyclic; and vii) substituted or unsubstituted C₁-C₂₀ heteroaryl.

The following are non-limiting examples of physiologically active agents releasable by the disclosed substrates. Antibiotics

Tn another embodiment, the disclosed substrates can release one or more of the following antibiotics:

Antibiotics that act mainly on Gram-positive bacteria: Phenoxymethylpenicillin potassium (Veetids); Oxacillin sodium (Bactocill); Benzylpenicillin potassium (Pfϊzerpen); Phenethicillin potassium (Syncillin);

Flucloxacillin sodium (Floxapen); Propicillin potassium; Benzylpenicillin benzathine hydrate (Bicillin L-A); Meticillin sodium (Staphcillin); Hetacillin potassium (Hetacin-K);

Phenoxymethylpenicillin benzathine; Clindamycin phosphate (Cleocin); Clindamycin palmitate hydrochloride (Cleocin pediatric); Clindamycin hydrochloride (Cleocin hydrochloride); Lincomycin hydrochloride (Lincocin); Vancomycin (Vancoled); Quinupristin; Dalfopristin; Quinupristin - dalfopristin mixt; (Synercid); Novobiocin sodium (Albamycin); Arbekacin sulfate (Habekacin);Teicoplanin (Tagocid); and Mupirocin calcium hydrate (Bactroban); Antibiotics that act mainly on Gram-negative bacteria: Carindacillin sodium (Geocillin); Pivmecillinam hydrochloride (Melysin); Carfecillin sodium; Aztreonam (Azactam); Carumonam sodium (Amasulin); Tobramycin (Tobracin); Amikacin sulfate (Amikin); Kanamycin monosulfate (Kantrex); Paromomycin sulfate (Humatin); Isepamicin sulfate (Isepacin); Spectinomycin hydrochloride (Trobicin); Colistin sodium methanesulfonate (Coly-Mycin M); Polymixin B sulfate (Aerosporin); and Ceftibuten (Cedax);

Antibiotics that act mainly on both Gram-positive bacteria and Gram-negative bacteria: Anhydrous ampicillin (Omnipe); Amoxicillin hydrate (Amoxil); Piperacillin sodium (Pentcilli); Bacampicillin hydrochloride (Spectrobid); Ampicillin hydrate (Amcill); Ciclacillin (Cyclapen-W);

Sultamicillin tosilate (Unasy); Lenampicillin hydrochloride (Valacilli); Ampicillin sodium (Omnipen); Carbenicillin sodium (Geope); Talampicillin hydrochloride (Aseocilli); Mezlocillin sodium (Mezli); Ticarcillin sodium £Ticar); Aspoxicillin (Doyle); Cefaclor (Alenfral); Cefadroxil (Sumacef); Cefixime (Suprax); Cefotetan; Cefalexin

(Keflex); Cefradine (Anspor); Cefazolin sodium (Ancef); Cefalotin sodium (Kefli);

Cefapirin sodium (Cefadyl); Cefmetazole sodium (Zefazone); Cefoxitin sodium (Mefoxi); Cefuroxime axetil (Cefti); Cefuroxime sodium (Zinacef); Cefdinir; (Cefzo);

Cefoperazone sodium (Cefobid); Cefotaxime sodium (Clafora); Cefpodoxime proxetil (Vanti); Ceftazidime (Fortaz); Ceftizoxime sodium (Cefizox); Ceftriaxone sodium (Rocephi); Cefluprenam N); Cefaloridine (Kefloridi); Cefepime dihydrochloride • (Maxipime); Cefacetrile sodium (Celtol); Ceφirome sulfate (Cefrom); Cefotiam hexetil hydrochloride (Pansporin-T); Ceftezole sodium (Celosli); Cefpimizole sodium AAjicef);

Cefditoren pivoxil (Meiact); Cefetamet pivoxil hydrochloride (Cefyl); Cefcapene pivoxil hydrochloride hydrate (Flomox); Cefovecin sodium; Cefteram pivoxil (Tomiro);

Cefuzonam sodium; Cefbuperazone sodium (Keiperazo); Cefotiam hydrochloride (Cerado); Cefodizime sodium (Kenicef); Cefpiramide sodium A(Suncefal); Ceftninox sodium (Meiceli); Cefaloglycin; Cefmatilen hydrochloride hydrate; Cefsulodin sodium (Takesuli); Cefamandole sodium (Kefdole); Cefazolin sodium hydrate; Cefotetan sodium (Cefota); Cefoselis sulfate (Winsef); Cefozopran hydrochloride (Firstci); Propylene glycolate cefatrizine (Seapuro); Cefroxadine (Oraspor); Flomoxef sodium (Flumari); Latamoxef sodium (Moxam); Netilmicin sulfate (Netromyci); Gentamicin sulfate (Garamyci); Dibekacin sulfate (Panimyci); Micronomicin sulfate (Sagamici); Bekanamycin sulfate (Kanendomyci); Astromicin sulfate (Fortimici); Sisomicin sulfate (Sisepti); Ribostamycin sulfate Vistamyci); Fosfomycin calcium Fosmici); Fosfomycin sodium (Fosmicin S); Imipenem hydrate; Amoxicillin - potassium clavulanate combination; (Clavamox); Imipenem hydrate - cilastatin sodium (Primaxi); Piperacillin sodium (Pentcilli); Tazobactam; Panipenem; Biapenem (Omegaci); Doripenem hydrate;

Faropenem sodium (Farom); Ampicillin sodium (Omnipen); Cilastatin sodium; Meropenem trihydrate (Merrem); Sulbactam sodium; Piperacillin hydrate; Clavulanate potassium; Piperacillin-tazobactam combination (Tazoci); and Panipenem-betamipron (Carbeni). Fragrance or Perfume Ingredients

In another embodiment, the disclosed substrates can release one or more of the following fragrance raw materials: 2,4-dimethyl-3-cyclohexene-l -methyl, 2,4-dimethyl cyclohexane methyl, 5,6-dimethyl-l-methylethenyl-bicyclo[2.2.1]hept-5-ene-2-methyl, 2,4,ό-trimethyl^;;3-cyclohexene- 1 -methyl, 4-( 1 -methylethyφcyciδhexyϊmethyl, a-T,3 - • ^■•^■■ trimethyl-2-norboranylmethyl, l,l-dimethyl-l-(4-methylcyclohex-3-enyl)methyl, ethyl,-2- phenylethyl, 2-cyclohexylethyl, 2-(o-methylphenyl)ethyl, 2-(m-methylphenyl)ethyl. 2-(p- methylphenyl)ethyl, 6,6-dimethylbicyclo[3.1.1 ]hept-2-ene-2-ethyl, 2-(4- methylphenoxy)ethyl, 3,3-dimethyl-Δ²-β-norbornanylethyl. 2-methyl-2-cyclohexylethyl, 1- (4-isopropylcyclohexyl)eιhyl, 1 -phenyl- 1-hydroxyethyl, l,l-dimethyl-2-phenylethyl, 1,1- dimethyl-2-(4-methylphenyl)ethyl, propyl, 1-phenylpropyl, 3-phenylpropyl, 2- phenylpropyl, 2-(cyclododec>l)-propan-l-yl, 2,2-dimethyl-3-(3-methylphenyl)propan-l-yl, 2-methyl-3-phenylpropyl, 3-phenyl-2-propen-l-yl, 2-methyl-3-phenyl-2-propen-l-yl, α-n- pentyl-3-phenyl-2-propen-l-yl, ethyl-3-hydroxy-3-phenyl propionate, 2-(4-methylphenyl)- 2-propyl, butyl, 3-methylbutyl, 3-(4-methylcyclohex-3-ene)butyl, 2-methyl-4-(2,2,3- trimethyl-3-cyclopenten- 1 -yl)butyl, 2-ethyl-4-(2,2,3-trimethylcyclopent-3-enyl)-2-buten- 1 - yl, 3-methyl-2-buten-l-yl, 2-methyl-4-(2,2,3-trimethyl-3-cyclopenten-l-yl)-2-buten-l -yl, 3- hydroxy-2-butanόhe, ethyl 3-hydroxybutyrate, 4-phenyl-3-buten-2-yl, 2-methyl-4- phenylbutan-2-yl, 4-(4-hydroxyphenyl)butan-2-one, 4=(4-hydroxy-3-methoxyphenyl)butan- 2-one, pentyl, cis-3-pentenyl, 3-methylpentyl, 3-methyl-3-penten-l-yl, 2-methyl-4- phenylpentyl, 3-methyl-5-phenylpentyl, 2-methyl-5-phenylpentyl, 2-methyl-5-(2,3- dimethyltricyclo-[2.2.1.0(2,6)]hept-3-yl)-2-penten-l -yl, 4-methyl- 1 -phenyl-2-pentyl, (1 - methyl-bicyclo [2.1.1 Jhepten-2-yl)-2-methylpent-l -en-3-yl, 3-rnethyl- 1 -phenylpent-3-yl, 1 ,2-dimethyl-3-( 1 -methylethenyl)cyclopent- 1 -yl, 2-isopropyl-4-methyl-2-hexenyl, cis-3- hexen-1-yl, trans-2-hexen-l-yl, 2-isopropenyl-5-methyl-4-hexen-l-yl, 2-ethyl-2-prenyl-3- hexenyl, 2-ethylhexyl, l-hydroxymethyl-4-isopropenyl-l-cyclohexenyl, l-methyl-4- isopropenylcyclohex-6-en-2-yl, ό-methyl-S-isopropenylcyclohex- 1 -yl, 1 -methyl-4- isopropenylcyclohex-3-yl, 4-iso-propyl-l-methylcyclohex-3-yl, 4-tert-butylcyclohexyl, 2- tert-butylcyclohexyl, 2-tert-butyl-4-methylcyclohexyl, 4-isopropylcyclohexyl, 4-methyl-l- ( 1 -methylethyO-S-cyclohexen- 1 -yl, 2-(5,6,6-trimethyl-2-norbomyl)cyclohexyl, isobomylcyclohexyl, 3,3,5-trimethylcyclohexyl, l-methyl-4-isopropylcyclohex-3-yl, 1,2- dimethyl-3 -(I -methyl ethyl)-cyclohexan-l-yl, heptyl, 2,4-dimethylhept-l-yl, 2,4-dimethyl- 2,6-heptandienyl, 6,6-dimethyl-2-oxymethylbicyclo[3.1.1 ]hept-2-en- 1 -yl, 4-methyl-2,4- heptadien-1-yl, 3,4,5,6,6-pentamethyl-2-heptyl, 3,6-dimethyl-3-vinyl-5-hepten-2-yl, 6,6- dimethyl-3-hydroxy-2-methylenebicyclo[3.1.1]heptyl, l,7,7-trimethylbicyclo-[2.2.1]hept-2- yl, 2,6-dimethylhept-2-yl, 2,6,6-trimethylbicyclo[1.3.3]hept-2-yl, octyl, 2-octenyl, 2- methyloctan-2-yl, 2-methyl-6-methylene-7-octen-2-yl, 7-methyloctan-l-yl, 3,7-dimethyl-6- octenyl, 377-dimethyl-7-ec'tenyl, 3,7-dimethyl-6-octen-l-y£ 3,7-dimethyl-2,ό^~-octadien-l-yl, 3,7-dimethyl-2,6-octadien-l-yl, 3,7-dimethyl-l,6-octadien-3-yl, 3,7-dimethyloctan-l-yl,.

3,7-dimethyloctan-3-yl, 2,^-octadien-l-yl, 3,7-dimethyl-6-octen-3-yl, 2,6-dimethy]-7-octen- 2-yl, 2,6-dimethyl-5,7-octadien-2-yl, 4,7-dimethyl-4-vinyl-6-octen-3-yl, 3-methyloctan-3- yl, 2.ό-dimethyloctan-2-yl, 2,6-dimethyloctan-3-yl, 3,6-dimethyloctan-3-yl, 2,6-dimethyl-7- octen-2-yl, 2,6-dimethyl-3,5-octadien-2-yl, 3 -methyl- l-octen-3-yl, 7-hydroxy-3,7- dimethyloctanalyl, 3-nonyl, 6,8-dimethylnonan-2-yl, 3-(hydroxymethyl)-2-nonanone, 2- nonen- l-yl, 2,4-nonadien-l-yl, 2,6-nonadien-l-yl, cis-6-nonen-l-yl, 3,7-dimethyl- l,6- nonadien-3-yl, decyl, 9-decenyl, 2-benzyl-M-dioxa-5-yl, 2-decen-l-yl, 2,4-decadien-l-yl, 4- methyl-3-decen-5-yl, 3,7,9-trimethyl-l,6-decadien-3-yl, undecyl, 2-undecen-l-yl, 10- undecen-1-yl, 2-dodecen-l-yl, 2,4-dodecadien-l-yl, 2,7,1 l-trimethyl-2,6,10-dodecatrien-l- yl, 3,7,1 l-trimethyl-l,6,10,-dodecatrien-3-yl, 3,7,1 l,15-tetramethylhexadec-2-en-l -yl, 3,7,11,15-tetramethylhexadec-l-en-3-yl, benzyl, p-methoxybenzyl, para-cymen-7-yl, A- methylbenzyl, 3,4-methylenedioxybenzyl, 2-(methyl)carboxy-l-hydroxyphenyl, 2- (benzyl)carboxy- 1 -hydroxyphenyl, 2-(cis-3-hexenyl)-carboxy- 1 -hydroxyphenyl, 2-(n- pentyl)carboxy- 1 -hydroxyphenyl, 2-(2 -phenyl ethyl)carboxy-l -hydroxyphenyl, 2-(ri- hexyl)carboxy-l -hydroxyphenyl, 2-methyl-5-isopropyl-l -hydroxyphenyl, 4-ethyl-2- methoxyphenyl, 4-allyl-2-methoxy- 1 -hydroxyphenyl, 2-methoxy-4-( 1 -propenyl)- 1 - hydroxyphenyl, 4-allyl-2,6-dimethoxy-l -hydroxyphenyl, 4-tert-butyl-l -hydroxyphenyl, 2- ethoxy-4-methyl-l -hydroxyphenyl, 2-methyl-4-vinyl-l -hydroxyphenyl, 2-isopropyl-5- methyl- 1 -hydroxyphenyl, 2-(isopentyl)-carboxy- 1 -hydroxyphenyl, 2-(ethyl)carboxy- 1 - hydroxyphenyl, 6-(methyl)carboxy-2,5-dimethyl-l ,3-dihydroxyphenyl, 5-methoxy-3- methyl- 1 -hydroxyphenyl, 2-tert-butyl-4-methyl- 1 -hydroxyphenyl, 1 -ethoxy-2-hydroxy-4- propenylphenyl, 4-methyl-l -hydroxyphenyl, 4-hydroxy-3-methoxybenzaldehyde, 2-ethoxy- 4-hydroxybenzaldehyde, decahydro-2-naphthyl, 2,5,5-trimethyl-octahydro-2-naphthyl, l,3,3-trimethyl-2-norbomyl, 3a,4,5,6,7,7a-hexahydro-2,4-dimethyl-4,7-methano-lH-inden- 5-yl, 3a,4,5,6,7,7a-hexahydro-3,4-dimethyl-4,7-methano-lH-inden-5-yl, 2-methyl-2-vinyl- 5-(l-hydroxy-l-methylethyl)tetrahydrofuranyl, and β-caryophyllenyl. Other Physiologically Actives hi another embodiment, the disclosed substrates can release one or more of the following naturally occuring flavors, inter alia, acetoin (acetyl methyl carbonol), agaric acid, α-ionone, amyl butyrate, benzaldehyde, 3,4-benzopyren, β-azarone, β-ionone, carvomenthenol, cinnamaldehyde, coumarin, ethyl acetate, ethyl butyrate, ethyl lactate, ethyl propionate, heliδtropine, hydrocuanic acid, hypercin, methyl cyclopentenόlone, methyl nonyl ketone, pulegone, quassine, quinine, safrole, spartein, thujone, and vanillin.' in another embodiment, the disclosed substrates can release one or more of the following artificial flavors, inter alia, α, α-dimethylphenethyl acetate, α, α- dimethylphenethyl butyrate, α, α-dimethylphenethyl formate, 3-methyl-4-phenyl-3-butene- 2-one, 4-emthyl-l-phenyl-2-pentanone, α-ethylbenzyl butyrate, isoeugenyl benzylether, α- isomethylionone, β-isomethylionone, α-methyl cinnamaldehyde, α-methyl ionone, β- methyl ionone, α-methyl lactate, α-methylbenzyl butyrate, α-methylbenzyl formate, α- methylbenzyl isobutyrate, α-methylbenzyl propionate, β-naptyl anthranilate, β-naptyl ethylether, β-naptyl isobutyl ether, α-terpinyl anthranilate, o-(ethoxymethyl) phenol, l-(p- methoxyphenyl)-l-penten-3-one, 1, 4-nonanediol diacetate, 1, 9-nonanedithiol, 1,2,3- tris(l'ethocy)-ethoxy-propane, 1,2-butanedi thiol, l,2-di(l'-ethoxyl) propane, 1,2- propanedithiol, 1,3-butanedithiol, 1,8-octanedithiol, 10-undecen-l -yl acetate, 10-undecenal, 1-ethylhexyl tiglate, l-phenyl-2 -propyl butyrate, l-phenyl-3 or 5-propylpyrazole, 2-(l- methylpropyl) thiazole, 2-(2-butyl)-4, 5-dimethyl-3-thiazoline, 2-(3-phenylpropyl) pyridine, 2-(3-phenylpropyl), tetrahydrofuran, 2-(p-tolyl)-propanal, 2, 6-nonadienal diethyl acetal, 2,3 or 10-mercaptopinane, 2,3-butanedithiol, 2,4-dimethyl-2-pentenoic acid, 2,4-dimethyl-5- acetylthiazole, 2,5-dimethyl-2, 5-dihydroxy-l, 4-dithiane, 2,5-dimethyl-3-furanthiol, 2,5- dimethyl-3-thioisovaleryfuran, 2,5-dimetyl -3-thofuroylfuran, 2,6,6-trimethyl-l-cyclohexen-

1 acetaldehyde, 2,6-dimethyl-3-(2-methyl-3-furyl) thio-4-heptanone, 2,6dimethyl-4- heptanol, 2,6-dimethyl-6-hepten-l-ol, 2,6-dimethyloctanal, 2-2-dithiodithiophene, 2-amyl-5 or keto-1, 4-dioxane, 2-benzofuran carbozaldehyde, 2-butyl-2-butenal, 2-butyl-5 or 6-keto- 1, 4-dioxane, 2-ethocythiazole, 2-ethyl-l, 3, 3-trimethyl-2-norbornanol, 2-ethyl-2-heptanal, 2-ethylbutyl acetate, 2-ethylthiophenol, 2-furan-methanethiol formate, 2-hexylidene cyclopentanone, 2-hydroxy-2-cyclohexen-l-one, 2-hydroxy-3, 5,5-trimethyl-2- cyclohexenone, 2-hydroxymethyl-6, 6-dimethyl-bioyclo (3,1,1) hept-2-enyl formate, 2- mercaptopropionic acid, 2-methoxy-5 or 6-isopropylpyrazine, 2-methyl 2-oxo-3- methylpentanoate, 2-methyl-3, 5 or 6-metnylthio-pyrazine, 2-methyl-3,5 or 6-furfurylthio- pyrazine, 2-methyl-3-furanthiol, 2-methyl-3-tolyl-propanal, 2-methyl-4-pentenoic acid, 2- methyl-4-phenyl-2-butanol, 2-methyl-4-pheylbutanal, 2-methyl-5-methoxythiazole, 2- meihylallyl but>τate, 2-methyloctanl, 2-methylundecanal, 2-pentyl-l-butan-3-one, 2-phenyl- f-propanol, 2-phenyl-3-(2-furyl)-prop-2-enal, 2-phenyl-3-carbethoxy furan, 2-phenyl-4- pentenal, 2-phenylpropanal, dimethyl acetal, 2-phenylpropionaldehyde, 2-phenylpropyl butyrate, 2-phenylpropyl isobutyrate, 2-pyridine methanethiol, 2-seo-butylcyclohexanone, 2-thienylmercaptan, 2-trans-6-trans-octadienal, 3-((2-mercapto- l-methylpropyl)thio)-2- . butanol, 3-((2-methyl-3-furyl)-thio)-4-heptanone, 3-(2-methylpropyl) pyridine. 3-(5- metrhyl-2-fαryl) butanal, 3-(hydroxymethyl)-2-heptanone, 3-(hydroxymethyl)-2-octanone, 3-(methylthio) butanal, 3-(p-isopropyl)-phenyl propanal, 3,5,5-trimethylhexanal, 3,5,5- trimethylhexanol, 3.7-dimethyl-2, 6-oxtadienyl 2-ethylbutyrate, 3-acetyl-2, 5-dimethylfuran. 3-acetyl-2,5-dimethylthiophene, 3-benzyl-4-heptanone, 3-ethyl-2-hydroxy-4-methyl- cyclopent-2-en-l-one, 3-heptyl-5-methyl-2(3H)-furanone, 3-mercapto-2-butanol, 3- mercapto-2-butanone, 3-mercapto-2-pentanone, 3-methyl-2-phenylbutanal, 3-methyl-5- propyl-2-cyclohexene-l-one, 3-octen-2-ol, 3-oxobutanal dimethyl aceta], 3-phenyl-4- pentenal, 3-phenylpropyl formate, 3-phenylpropyl hexanoate, 3-phenylpropyl isobutyrate, 3-phenylpropyl isovalerate, 3-phenylpropyl propionate, 4-((2-methyl-3-furyl)-thio)-5- nonanone, 4-(methylthio) butanal, 4-(methylthio) butanol, 4-(methylthio)-2-butanone, 4- (methylthio)-4-methyl-2-pentanone, 4-(p-acetoxyphenyl)-2-butanone, 4,4-dibutyl-y- butyrolactone, 4,5-dimethyl-2-ethyl-3-thiazoline, 4,5-dimethyl-2-isobutyl-3-thiazoline,4- acetyl-6-t-butyl-l, 1-dimethylindane, 4-heptanal diethyl acetal, 4-mercapto-2-butanone, A- methyl-2-pentyl-l, 3-dioxolane, 4-methyl-5-thiazoleethanolacetate, 4-methylbiphenyl, 4- phenyl-2-butyl acetate, 5- decenoic acid, 6-decenoic acid, 5-methoxy-3-ethyl-pyrazine, 6- methoxy-3 -ethyl -pyrazine, 5 -methoxy-3 -methyl-pyrazine, 6-m ethoxy-3 -methyl -pyrazine, 5,7-dihydro-2-methylthieno (3,4-d) pyrimidine, 5-ethyl-2-hydroxy-3-methyl-cyclopent-2- en-l-one, 5-methyl-5-hexen-2-one, 5-phenyl-pentanol, 6-hydroxy-3, 7-dimethyloctanoic acid lactone, 6-methyl coumarin, 6-octenal, 7-ethoxy-4-methyl-coumarin, 7-methyl- 4,4a,5,6-tetrahydro-2(3H)-naphthalenone, 9-undecenal, acetaldehyde benzyl methoxyethyl acetal, acetaldehyde butyl phenethyl acetal, acetaldehyde disopropyl acetal, acetaldehyde phenethyl propyl acetal, acetyl nonanoyl (2,3-undecadione), allyl 2-ethylbutyrate, allyl acetic acid (pentenoic acid), allyl anthranilate, allyl butyrate, allyl cinnamate, allyl crotonate, allyl cyclohexylacetate, allyl cyclohexylbutyrate, allyl cyclohexylhexanoate, allyl cyclohexylvalerate, allyl furoate, allyl heptanoate, allyl hexenoate, allyl isovalerate, allyl nonanoate, allyl octanoate, allyl phenoxyacetate, allyl phenylacetate, allyl propionate, allyl. sorbate, allyl thiopropionate, allyl tiglate, allyll undecen-10-oate, allyl -x-ionone, anisyl phenylacetate, anisyl propionate, anisylactenone, benzaldehyde glyceryl acetate, benzaldehyde propyleneglycol acetal, benzoin, benzyl 2, 3-dimethyl-crotonate, benzyl butyl ether, benzyl isobutyl carbinol, benzyl isobutyl ketone, benzyl isoeugegenyl ether, benzyl phenylacetate, benzyhpropyl carbinol, benzylidene-methional, benzylidene-methyl acetone, bis-(2,5-dimethyl-3-furyl) disulphide, bis-(2-methyl-3-furyl) disulphide, bis-(2-methyl-3- furyl) tetrasulphide, butan-3-one-2-y] butanoate, butyl 10-undecenoate, butyl 2-decenoate, butyl acetoacetate, butyl anthranilate, butyl butyrylglycollate, butyl butyryl lactate, butyl cinnamate, butyl ethyl malonate, butyl levulinato, carvacryl ethylether, carvyl propionate, caryophylene alcohol acetate, cedryl acetate, cinnamaldehyde ethyleneglycol acetal, cinnamyl formate, cinnamyl isobutyrate, cinnamyl phenylacetate, cinnamyl propionate, cis- 5-isopropenyl-cis-2-methylcyclo-pentan- l-carboxaldehyde, citral diethyl acetal, citral dimethyl acetal, citral propyleneglycol acetal, citronellyl oxyacetaldehyde, citronellylphenylacetate, cyclocitral, cyclohexanecarboxylic acid, cyclohexyl acetic acid, cyclohexyl actetate, cyclohexyl anthranilate, cyclohexyl formate, cyclohexyl hexanoate, cyclohexyl isovalerate, cyclohexyl meroaptan, cyclohexyl methyl pyrazine, cyclohexyl propionate, cyclohexylbutyrate, cyclohexylcinnameta, cyclohexylethyl acetate, cyclopentanethiol, δ- damascone, δ-decalactone, decanal dimethyl acetal, dehydrodihydroinone, dehydrodihydroionol, di-(butan-3-one-l-yl) sulphide, diallyl polysulphide, dibenzyl disulphide, dibenzyl ether, dibenzyl ketone (l,3-diphenyl-2-propanone), dibutyl sebacate, dicyclohexyl disulphide, diemthyl phenylethyl carbinyl acetate, diethyl sebacate, dimethyl phenyl carbinyl isobutyrate, dimethyl phenylethyl carbinyl isobutyrate, diphenyl disulphide, dodeca-3, 6-dienal, -dodecalactone, dodecyl isobutyrate, ethyl 10-undecenoate, ethyl 2,4- dioxohexanoate, ethyl 2-acetyl-3-phenylpropionate, ethyl 2-ethyl-3-phenylpropanoate, ethyl 2-methyl-3, 4-pentadienoate, ethyl 2-methyl-3-pentencate, ethyl 2-methyl-4-pentenoate, ethyl 2-methylpentanoate, ethyl 3-(furfrylthio) propionate, ethyl 3-oxohexanoate, ethyl 4- (methylthio)-butyrate, ethyl 4-phenylbutyrate, ethyl aconitate, ethyl benzoylacetate, ethyl butyryllaciate, ethyl cresoxyacetate, ethyl cyclohexanecarboxylate, ethyl cyclohexylproprionate, ethyl furylpropionate, ethyl isoeugenyl ether (isoeugenyl ethyl ether), ethyl maltol, ethyl methyl phenyl glycidate, ethyl n-ethylanthranilate, ethyl nitrite, ethyl octine carnonate (ethyl 2-nonynoate), ethyl phenylglycidate, ethyl-2- mercaptopropionate, ethyleneglycol tridecanedioic acid cyclic diester, ethylvanillin, eugenyl formate, furfuryl isopropyl sulphide, -furfuryl octanoate, furfuryl thipropionate, furfurylidene butanal, geranyl acetoacetate, geranyl phenylacetate, glucose pentaacetate, glyceryl 5-hydroxydecanoate, glyceryl 5-hydroxydodecanoate, guaiacyl phenylacetate, guaiyl acetate, heptanal dimethyl acetal, heptanal glyceryl acetal (2-hexyl-4- hydroxymethyl-1, 3-dioxolon and 2-hexyl-5 -hydroxy- 1, 3-dioxane), heptyl cinnamate, hexyi 2-furoate, fiexyl 2-methyl-3(4)-pentenoate, hydroquinone monoethyl ether, hydroxycitrondlal, hydroxycitronellal diethyl acetal, hydroxycitronellal dimethyl acetal, isoamyl acetoacetate, isoamyl cinnamate, isoamyl furylbutyrate, isoamyl furylpropionate, isoamyl pyruvate, isobornyl acetate, isobornyl anthranilate. isobomyl butyrate, isobornyl cinnamate, isobomyl foπnate, isobomyl isovalerate, isobornyl phenylacatate, isobornyl propionate, isobutyl acetoacetate, isobutyl furyi propionate, isobutyl phenylacetate, isobutyl salicylate, isoeugenyl acetate, isoeugenyl butyl ether, isoeugenyl foπnate, isoeugenyl phenylacetate, isojasmone, isopropyl cinnamate, isopropyl phenylacetate, isopropyl tiglate, isoquinoline, linalyl anthraniate, linalyl cinnamate, linalyl phenylacetate, maltyl isobutyrate, methoxypyrazine, methyl β-naphthyl ketone, methyl 1-acetoxycyclohexy ketone, methyl 4- (methylthio) butyrate, methyl 4-phenylbutyrate, methyl docine carbonate, methyl furfuracrylate, methyl heptine carbonate, methyl octine carbnonate, methyl p-tert- butylphenylactate, methyl styryl carbinol, methyl-isobutylcarbinyl acetate, -methyl-p- methoxy-cinnamaldehyde, n-ethyl-2-isopropyl-5 -methyl-cyclohexane carboxamide, nonanediol acetate, octanal dimethyl acetal, octyl formate, octyl phenylacetate, octylheptanoate, o-propylphenol, o-tolyl acetate, o-tolyl isobutyrate, o-tolyl salicylate, pentyl 2-furyl ketone, peperonyl acetate, p-ethoxybenzaldehyde, phenethyl 2-furoate, phenethyl anthranilate, phenetyl seneciate, phenoxyacetic acid, phenoxyethyl osibutyrate, phenyl ethyl methyl ethyl carbinol (l-phenyl-3-methyl-3-pentanol), phenylacetal dehyde 2, 3-butylene-glycol acetal, phenylacetaldehyde diisobutyl acetal, phenylacetaldehyde glycery acetal, phenylethyl methyl caminol (4-phenyl-2-butanol), piperonyl acetone, piperonyl isobutyrate, p-isopropyl phenyl acetaldehyde, p-methyl cinnamaldehyde, p-methylbenzyl acetone (4-(p-tolyl)-2-butanone), potassium 2- (r-ethoxy)ethoxypropanoate, p-propyl anisole, propenylguaethol, propyl 2-furoate, propyl 2-mefhyl-3-furyl disulphide, propyl cinnamate, propyl furylacrylate, propyl thioacetate, propylene glycol dibenzoate, pseudo- cyclocitral, p-tolyl 3-methylbutyrate, p-tolyl isobutyrate, p-tolyl laurate, p-tolyl octanoate, p-tolyl phenylacetate, pyrazine ethanethiol, pyrazine methanethiol, pyrazinyl methyl sulphide, resorcinol dimethyl ether, rhodinyl acetate, rhodinyl isovalerate, rhodinyl phenylacetate, rhodinyl propionate, santalyl acetate, santalyl phenylacetate, s-methyl ionone, spiro (2,4-dithia-l-methyl-8-oxabicyclo (3,3,0) octane-3, 3'-(l'-oxa-2'-methyl)- cyclopentane), sucrose octaacetate, t-2-octenyl butanoate, terpinyl cinnamate, terpinyl isobutyrΛte, teφinyl isovalerate, tetrahydrofurfuryl acetate, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, tetrahydrolianlool, tetrahydro- pseudo-ionone, tetramethyl ethylcyclohexenone,

glyceryl acetal, trans-3-heptenyl acetate, trans-3-heptenyl isobutyrate, tributyl acetylcitrate, vanillin acetate, vanillin isobutyrate. vanillylidene acetone, vetiveryl acetate, x-amylcinnamaldehyde dimethyl acetal, x-amylcinnamic aldehyde, x-amylcinnamyl acetate, x-amylcinnamyl alcohol, x-ainylcinnamyl formate, x-amylcinnamyl isovalerate, and x-butylciniiamaldehyde. Tn one embodiment, the disclosed substrates can release one or more of the following pharmaceutical actives: atorvastatin ([R-(R*, R*)]-2-(4-fluorophenyl)-beta,delta- dihydroxy-5-(l-methylethyl)-3-phenyl-4- [(phenylamino)carbonyl]-lH- pyrrole- 1-heptanoic acid); montelukast (2-[l-[[(lΛ)-l-[3-[2-(7-chloroquinolin-2-yl)ethenyl]phenyl]-3-[2-(2- hydroxypropan-2-yl)phenyl]propyl]sulfanylmethyl]cyclopropyl]acetic acid); escitalopram (S-(+)- 1 -[3-(dimethylamino)propyl]- 1 -(p-fluorophenyl)-5-phthalancarbonitrileoxalate); esomeprazole ((5)-5-methoxy-2-[(4-methoxy-3,5-dimethylpyridin-2-yl)methylsulfinyl]-3H- benzoimidazole); levofhyroxine (3,5,3',5'-tetraiodo-l-thyronine); clopidogrel ((+)-(S)-mefhyl 2-(2-chlorophenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate); metoprolol (l-[4- (2-methoxyethyl)-phenoxy]-3-propan-2-ylamino-propan-2-ol); lansoprazole (2-[(3-methyl- 4-(2,2,2-trifluoroethoxy) pyridin-2-yl)methylsulfinyrj-lH-benzoimidazole); ezetimibe ((3/?,4₁S)-] -(4-fluorophenyl)-3-((35)-3-(4-fluorophenyl)-3-hydroxypropyl)-4-(4- hydroxyphenyl)-2-azetidinone); simvastatin ([(15',3/?,7/?,85,8αi?)-8-[2-[(2/?,4Λ)-4-hydroxy- 6-oxo-oxan-2-yl]ethyl]-3,7-dimethyl-l,2,3,7,8,8α-hexahydro-naphthalen-l-yl]2,2- dimethylbutanoate); fluticasone (S-(fluoromethyl) (6S,SS,9R,- 1 OS, US,\ 3S, 145, 16R, 17R)- 6,9-difluoro-l l,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,l 1,12,14,15,16- octahydrocyclopenta-[α]phenanthrene-17-carbothioate); cetirizine ((±)-[2-[4-[ (4- chlorophenyl)phenylmethyl]-l- piperazinyljethoxy] acetic acid); venlafaxine (l-[2- dimethylamino-1- (4-methoxyphenyl)- ethyl]cyclohexan-l-ol); pantoprazole (5- (difluoromethoxy)- 2-[(3,4-dimethoxypyridin-2-yl) methylsulfinyl]- 3H-benzoimidazole); valsartan (N-(I -oxopentyl)-N-[[2 '-(lH-tetrazol-5-yl) [1,1 '-biphenyl]-4-yl]methyl]-l-valine); alendronate (sodium [4-amino-l -hydroxy- l-(hydroxy-oxido-phosphoryl)- butyl]phosphonic acid); rosuvastatin (7-[4-(4-fluorophenyl)-6-(l -methylethyl)-2-(methyl-methylsulfonyl- amino)-pyrimidin-5-yl]-3,5-dihydroxy-hept-6-enoic acid); levofloxacin ((-)-(5)-9-fluoro- 2,3-dihydro-3-methyl-l0-(4-methyl-l-piperazinyl)-7-oxo-7H-pyrido[l,2,3-de]-l,4- benzoxazine-6-carboxylic acid); valsartan (3-methyl-2- [pentanoyl-[ [4-[2-(2H-tetrazol-5- yl) phenyl] phenyl] methyl]amino] -butanoic acid); duloxetine ((+)-(5)-N-methyl-3- (naphthalen- 1 -yloxy)-3-(thiophen-2-yl)propan- 1 -amine); pioglitazone (5-((4-(2-(5-ethyl-2- pyridiήyl)ethoxy)phenyl)methyl)-(+)-2,4-thiazolidinedione); celecoxib (4-[5-(4- methylphenyl)-3-(trifluoromethyl)pyrazol-l-yl]benzenesulfonamide); tamsulosin ((/?)-5-(2- (2-(2-ethoxyphenoxy)ethylamino)propyl)-2-methoxybenzenesulfonamide); quetiapine (2- (2-(4-dibenzo[6./][l,4]thiazepine- l l-yl-l-piperazinyl)ethoxy)ethanol); amlodipine (3-ethyl- 5-methyl-2-(2 -aminoethoxymethyl)-4-(2-chlorophenyl)- 1 ,4-dihydro-6-methyl-3,5- pyridinedicarboxylate); fenofibrate (l-methylethyl-2-[4-(4-chlorobenzoyl)phenoxy]- 2- methyl-propanoate); sildenafil (1 -[4-ethoxy-3-(6.7-dihydro-l -methyl-7-oxo-3-propyl-lH- pyrazolo[4,3 -cTjpyrimidin-5 -yl)phenylsulfonyl] -4-methylpiperazine citrate) ; ramipril ((15,55,75)-8-[(25)-2-[[(15)-l-ethoxycarbonyl->-phenyl-propyl]amino]propanoyl]-8- azabicyclo[3.3.0]octane-7-carboxylic acid); risedronate ((I -hydroxy- l-phosphono-2- pyridin-3-yl-ethyl)phosphonic acid); Zolpidem (N,N-6-trirnethyl-2-(4-methylphenyl)- imidazo(l,2-α)pyridine-3-acetamide); losartan ((l-((2'-(2H-tetrazol-5-yl)biphenyl-4- yl)methyl)-2-butyl-4-chloro-l//-imidazol-5-yl)methanol); carvsditol (1 -(9//-carbazol-4- yloxy)-3-[2-(2-methoxyphenoxy)ethylamino]propan-2-ol); valaciclovir(2-[(2-amino-6-oxo- 3 ,9-dihydropurin-9-yl)methoxy] ethyl-2-amino-3 -methyl-butanoate) ; pregabalin ((5)-3 - (aminomethyl)-5-methylhexanoic acid); methylphenidate (methyl 2-phenyl-2-(2- piperidyl)acetate); Risperidone (4-[2-[4-(6-fluorobenzo[c(]isoxazol-3-yl)-l-piperidyl]ethyl]_/- S-methyl^.ό-diazabicyclo^^.OJdeca-l^-dien-S-one); topiramate (2,3:4,5-bis-O-(l- methylethylidene)-beta-d-fructopyranose sulfamate); varenicline (7,8,9, 10- tetrahydro-6,10- methano-6H-pyrazino(2,3-h)(3)benzazepine); rosiglitazone (5-((4-(2-(methyl-2- pyridinylamino)ethoxy)phenyl)methyl)- 2,4-thiazolidinedione); paclitaxel (( 1 S,2S,3RAS,7R,9S, 1 OS, 12R,15S) -4, 12-diacetoxy- 15 - { [(2R,3S)-3- (benzoylamino)-2- hydroxy-3- phenylpropanoyl]oxy} - 1 ,9- dihydroxy- 10,14,17,17-tetramethyl - 11 -oxo-6- oxatetracyclo[l 1.3.1.0-3, 10~.0~4,7~] heptadec-13-en-2-yl benzoate); olanzapine (2- methyl-4-(4-methyl-l-piperazinyl)-10H-thieno[2,3-b][l,5]benzodiazepine); sertraline ((IS)- cis-A-(3 ,4-dichlorophenyl)- 1 ,2,3 ,4-tetrahydro-

/V-methyl- 1 -naphthalenamine); paroxetine ((35'-trans)-3-(( 1 ,3-benzodioxol-5-yloxy)methyl)- 4-(4-fluorophenyl)-piperidine); bupropion ((±)-2-(tert-butylamino)- 1 -(3- chlorophenyl)propan-l-one); citalopram (l-[3-(dimethylamino)propyl]-l-(4-fluorophenyl)- l,3-dihydro[2]benzofuran-5-carbonitrile)); sumatriptan (l-[3-(2-dimethylaminoethyl)-lH- indol-5-yl]-N-methyl-methanesulfonamide); fluconazole (2-(2,4-difluorophenyl)-l,3- ό/5(lH-l,2,4-triazol-l-yl)propan-2-ol); mycophenolic acid ((e)-6-(4-hydroxy-6-methoxy-7- methyl-3-oxo-l,3-dihydroisobenzofuran-5-yl)-4-methylhex-4-enoic acid); rabeprazole (2- [(4-(3imetltoxypropoxy)- 3-methyl-pyridin-2-yl)^;ethyl-sulfinyl3-l/f-benzoimidazole); • . cerbinafine ((s)-iV,6,6-trimethyl-Λ'^:-(naphthalen-l-ylmethyl)hept-2-en-4-yn-l -amine); lamotrigine (6-(2.3-dichlorophenyl)-l,2,4-triazine-3,5-diamine); zoledronic acid ((1- hydroxy-2-imidazol-l-yl-l-phosphono-ethyl)phosphonic acid); candesartan (3-((2'-(2//- tetrazol-5-yl)biphenyl-4-yl)methyl)-2-ethoxy-3H-benzo[d]imidazole-4-carboxylic acid); famotidine (2-[4-[2-(amino-sulfamoylimino-methyl)ethylsυlfanylmethyJ]-l ,3-thiazol-2- yl]guanidine); valdecoxib (4-(5-methyl-3-phenylisoxazol-4-yl)benzene-sulfonamide); fluoxetine (N-methyl-3-phenyl-3-[4-(trifluoromethyl)phenoxy]-proρan-l-amine); doxazosin ( 1 -(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-( 1 ,4-benzodioxan-2-ylcarbonyl) piperazine methanesulfonate); mirtazapine ( 1 ,2,3 ,4, 10, 14b-Ηexahydro-2-methylpyrazino[2, 1 - α]pyrido[2,3-c][2]benzazepine); efavirenz (8-chloro-5-(2-cyclo-propylethynyl)- 5- (trifluoromethyl)- 4-oxa-2-azabicyclo [4.4.0]deca- 7,9,1 l-trien-3-one); felodipine (ethyl methyl 4-(2,3-dichlorophenyl)- 1 ,4-dihydro-2,6-dimethyl-3,5- pyridinedicarboxylate); ranitidine ((e)-N-(2-((5-((dimethylaminomethyl)furan-2-yl)methylthio)ethyl)-N'-methyl-2- nitroethene- 1,1 -diamine); amphetamine (l-phenyl-propan-2-amine); anastrozole (2-[3-(l- cyano-1-methyi-ethyl)- 5-(l//-l,2,4-triazol-l -ylmethyl)phenyl]- 2-methyl- propanenitrile); dorzolamide (2-ethylamino-4-methyl-5, 5-dioxo-5$l^Λ{6}, 7-dithiabicyclo[4.3.0] nona-8,10- diene-8-sulfonamide); lamivudine (l-2',3'-dideoxy-3'-thiacytidine); ziprasidone (5-[2-[4- (l,2-benzisothiazol-3-yl)-l-piperazinyl]ethyl]-6-chloro-l,3-dihydro-2H-indol-2-one); nevirapine (l-cyclopropyl-Sjl

[3,2-b:2',3'-e][l,4] diazepin- 6-one); and zolmitriptan ((45)-4-{[3-(2-dimethylaminoethyl)-lH-indol-5-yl]methyl}-l,3- oxazolidin-2-one).

In another embodiment, the disclosed substrates can release one or more of the following pharmaceutical actives: atorvastatin calcium, amlodipine besylate, pravastatin, venlafaxine, gabapentin, omeprazole, losartan, clopidogrel bisulphate, valsartan, azithromycin, sodium montelukast, fexofenadine hydrochloride, sodium enoxaparin, ciprofloxacin hydrochloride monohydrate, docetaxel, clopidogrel bisulphate, quetiapine fumarate, sodium pravastatin, potassium amoxicillin-clavulanate, metoprolol, sodium pantoprazole, clarithromycin, ramipril, fluconazole, levofloxacin, gemcitabine, budesonide, zidovudine, raloxifene hydrochloride, nifedipine, candesartan cilexetil, tacrolimus, fluvastatin, tamsulosin hydrochloride, quinapril ydrochloride, peginterfron, piperacillin tazobactam, imipenem sodium cilastatin, levofloxacin, sodium diclofenac, ramipril, lisinopril, sodium fosinopril, ezetimibe, benazepril hydrochloride, and meropenem. TSs following is an example of the preparation of a disclosed substrate. Scheme I

Reagents and conditions: (a) acetonitrile; 2 hr.

Reagents and conditions: (b) BF₃, acetonitrile, rt, 24 hr.

EXAMPLE 1

I - {4,7, 10, 13-tetramethyl- 1 -(2-phenyl- 1 ,3-dioxolan-4-yl)-2-[(2-phenyl- 1 ,3-dioxolan-4- yl)methyl] -6,9, 12-trioxa-2-azatetradecan- 14-oxy} -2,2-bis-( {4,7, 10, 13-tetramethyl- 1 -(2- phenyl-l,3-dioxolan-4-yl)-2-[(2-phenyl-l,3-dioxolan-4-yl)methyl]-6,9,12-trioxa-2- azatetradecan- 14-oxy } methyl)butane

Preparation of 4,26-bis(2,3-dihydroxypropyl)-l 5-[ 11 -(2,3-dihydroxypropyl)- 13,14- dihydroxy-4,7,10-trimethyl-2,5,8-trioxa-l l-azatetradecyl)-l l,15-diethyl-5,8,19,22,25- pentamethyl-7,10,13,17,20,23-hexaoxa-4,26-diazanonacosane-l,2,28,29-tetraol: To a flask containing 12-( {2-[2-(2-aminopropoxy)propoxy]butoxy} methyl- 1 ,2-ethyl-5,8, 16,19- tetramethyl-4,7, 10, 14, 17,20-hexaoxatricosane-2,22-diamine (JEFF AMINE™ T5000 available from Huntsman Chemical Co.) (50 g) and acetonitrile in (75 mL). The solution was allowed to stir for 15 minutes. To a dried one-neck 250 mL flask equipped with a stir bar was added glycidol (3.99 mL) and acetonitrile (10 mL). The Jeffamine T5000 solution was then added dropwise with efficient stirring to the glycidol solution at a rate of 1 drop every 3 seconds. After the addition was complete, the reaction solution was allowed to stir for and additional 2 hours after which time the solvent was removed in vacuo to provide the Jeffamine-glycidol adduct 1.

Preparation of 1 - {4,7, 10, 13-tetramethyl- 1 -(2-phenyl- 1 ,3-dioxolan-4-yl)-2-[(2- phenyl- 1 ,3-dioxolan-4-yl)methyl]-6,9, 12-trioxa-2-azatetradecan- 14-oxy} -2,2-bis- ( {4,7, 10, 13-tetramethyl- 1 -(2-phenyl- 1 ,3 -dioxolan-4-yl)-2-[(2-phenyl- 1 ,3-dioxolan-4- yl)methyl]-6,9,12-trioxa-2-azatetradecan-14-oxy}methyl)butane 2: To a 250 mL flask was added the Jeffamine-glycidol adduct (10 g) and acetonitrile (100 mL). The mixture was stirred for 15 minutes. To a 250 mL 3-neck flask was added benzaldehyde dimethyl acetal (1.81 mL) in acetonitrile (15 mL) under an inert atmosphere of nitrogen. Boron trifluoride (0.04 mL) was added dropwise to the benzaldehyde solution via syringe. The solution of Jeffamine-glycidol was then added dropwise at a rate of 1 drop every 3 seconds. The solution was allowed to stir for 24 hours. The reaction solution was concentrated in vacuo to afford the desired active substrate 2. The following provides an example of combining the active substrate 2 with a •^'" cellulosic material to form a regenerated cellulose matrix.

Microcrystalline cellulose (1 g) [10 wgt %] was dissolved in l-methyl-3- butylimidazolium chloride (10 g) using microwave pulse heating. The solution was allowed to cool and the active substrate prepared according to the procedure above (2 g) was added and the solution was homogenized. Polypropylene glycol [MW=2000] is heated in a microwave for approximately 1 minute using 30 second pulses and an over head ultrahigh torque stirred is inserted and the solution stirred at 850 rpm. To the warm solution of polypropylene glycol was add the ionic liquid solution of microcrystalline cellulose. The solution was stirred for 30 minutes then immediately added to a like volume of ethanol. The resulting mixture is manually stirred reconstitute the composite which has separated out ;n the form of beads that were separated by filtration. The isolated beads are vacuum dried then washed with an addition 5 aliquots of ethanol (50 mL) followed by 5 aliquots of water (50 mL). The beads were stored in distilled water until utilized.

The following describes the characterization of the substrate piepared according to Example 1. The following data are provided to assist the formulatot in preparing the disclosed physiologically active agent-releasing substrates. ¹H NMR δ 1.05 δ 0.92

The following scheme outlines a further example of the preparation of a disclosed substrate.

Scheme II

Reagents and conditions: (a) PBr₃, pyridine.

Reagents and conditions: (b) NaCN, acetonitrile.

Reagents and conditions: (c) C₆H₅CH₂CH₂OH, H⁺; acetonitrile.

Regenerated Cellulose Matrix

The disclosed substrates can be delivered by combining the substrates with regenerated cellulose utilizing the methods described in co-pending U.S. Patent Application Serial Number 11/810,602 filed June 5, 2007 which is a Continuation Application of U.S. Patent Application Serial Number 11/475630 filed June 27, 2006 that claims priority to U.S. Provisional Application Serial Number 60/694,902 filed June 29, 2005.

The regenerated cellulose component of the disclosed composites can be prepared by methods described below. In general, the regenerated cellulose can be prepared by dissolving a starting cellulose in an ionic liquid and then adding to the solution a liquid non- solvent (i.e., a liquid that does not substantially dissolve the starting cellulose but is miscible with the ionic liquid). The starting cellulose can be any cellulosic material. Examples of suitable starting cellulose include, but are not limited to, fibrous cellulose, wood pulp, paper, linters, cotton, and the like, including mixtures thereof. This produces regenerated cellulose, which, in many cases, has substantially the same molecular weight as the starting cellulose from which it was prepared. By "substantially the same molecular weight" is meant that the difference in molecular weight between the starting cellulose and the regenerated cellulose is less than about 25%, 20%, 15%, 10%, 5%, 1%, or 0% of the molecular weight of the starting cellulose. Further, the regenerated cellulose can be substantially free of an increased amount of substituent groups relative to the starting ^• cellulose. By "substantially free of an increased amount of substituent groups" is meant that the number of substituent groups on the regenerated cellulose (e.g., functionalization of the hydroxyl groups present on cellulose by esterification or alkylation), commonly referred to as the degree of substitution or "D.S.," is less than, equal to, or 0.1, 0.5, 1, 5, 10, 15, 20, 25, 30, or 35% greater than that of the starting cellulose. Also, the regenerated cellulose component of the disclosed composites can be substantially free of entrapped ionic liquid degradation products. By "substantially free of entrapped ionic liquid degradation products" is meant that the regenerated cellulose can contain less than about 25%, less than about 20%, less than about 15%, less than about 10%, less than about 5%, less than about 3%, less than about 2%, less than about 1%, less than about 0.5%, or about 0% by weight of the regenerated cellulose of entrapped ionic liquid degradation products.

In many examples, the regenerated cellulose is in the form of a bead(s). It is noted that cellulose is not digestible, unlike current drug delivery matrixes. As such the cellulose composites disclosed herein can be expected, in certain applications, to be excreted from a body substantially unchanged, except for the release of the second active substance. Methods for the entrapment of the disclosed substrates in a cellulose matrix involve the dissolution and regeneration of ionic liquid (IL) / cellulose compositions. The regenerated cellulose that comprises the disclosed substrates can be derivatized with a linker that serves to crosslink two or more substrates thereby providing a more secure attachment of the substrate to the regenerated cellulosic material. In many examples, the linker crosslinks in a manner such that the substrate will not, or will be slow to, leach out of the regenerated cellulose matrix. An advantage of the disclosed methods is that the linking of the disclosed substrate can be performed in an ionic liquid, which can solubilize cellulose and active substrates. Other solvent systems can hydrolyze or otherwise render the substrate physiologically active inactive. These methods can provide for the incorporation of activity (e.g., biological or chemical) into cellulose products like paper and clothing. Further, it will be clear to those skilled in the art that the disclosed methods and composites are applicable to the preparation of various forms of composites, e.g., films, beads, particles, flakes, fibers, substrates, coatings, capsules, gels, and the like, in or on which substrates are entrapped.

The hydrophilic ionic liquid solution used herein can be substantially free of water, a water- or alcohol-miscible organic solvent, or nitrogen-containing base and contains soMBilized cellulose. Contemplated organic solvents of which the solution is fres-include solvents such as dimethyl sulfoxide, dimethyl formamide, acetamide, hexameihyl phosphoramide, water-soluble alcohols, ketones or aldehydes such as ethanol, methanol, 1- or 2-propanol, tert-butanol, acetone, methyl ethyl ketone, acetaldehyde, propionaldehyde, ethylene glycol, propylene glycol, the C₁-C₄ alkyl and alkoxy ethylene glycols and propylene glycols such as 2-methoxyethanol, 2-ethoxyechanol. 2-butoxyethanol, diethyleneglycol, and the like. Linkers

The disclosed substrates can be crossilnked to the regenerated cellulose matrix with a linker comprising a substituted or unsubstituted, branched or unbranched, alkyl, alkenyl, or alkynyl group, ether, ester, polyether, polyester, polyalkylene, polyamines, heteroatom substituted alkyl. alkenyl, or alkynyl group, cycloalkyl group, cycloalkenyl group, heterocycloalkyl group, or heterocycloalkenyl group. The linker can comprise from 1 to 20 atoms in length. /

In one embodiment, the linker comprises a Ci-C₆ branched or straight-chain alkyl, a Ci-C₆ branched or straight-chain alkoxyl, or a C₂-C₆ branched or straight-chain alkyl where one or more of the carbon atoms is substituted with oxygen or an amino group. Non- limiting examples include linkers that prior to crosslinking the substrate comprises a dialdehyde, paraformaldehyde, epoxide, a dione, a diester, or a diisocyanate, for example, 1,3-phenyldiisocyanate, 1 ,4-phenyldiisocyanate, 1 ,4-cyclohexyldiisocyanate, toluene diisocyanate, or 1 ,6-hexane-diisocyanate.

In another embodiment, linker prior to crosslinking the first active substrate comprises an organo-halide. In one example, the crosslinking agent is epichlorohydrin.

In a still further embodiment, the linker prior to crosslinking comprises a hydrazine, an amine, an alcohol, a carboxylate, or a thiol.

The disclosed composites further comprise substrates that are linked to one another. In one embodiment, the substrate is crosslinked to one or more other substrates with a linker, and the linker comprises a substituted or unsubstituted, branched or unbranched, alkyl, alkenyl, or alkynyl group, ether, ester, polyether, polyester, polyalkylene, polyamines, heteroatom substituted alkyl, alkenyl, or alkynyl group, cycloalkyl group, cycloalkenyl group, heterocycloalkyl group, or heterocycloalkenyl group. For example, the substrate is crosslinked to one or more other substrates with a linker, and the linker comprises a C₁-C₆ branched or straight-chain alkyl, a C₁-C₆ branched or straight-chain alkoxyl, or a C₂-C₆ branched or straight-chain alkyHvhere one or more of the carbon-atoms is substituted with ^• oxygen or an amino group. The substrates can be linked to one another by the same linkers that are used Ui link the substrates to the cellulose matrix. Ionic Liquids ^;

Ionic liquids are a class of solvents composed of ionized species in contrast to traditional organic or aqueous solvents which are molecular non-ionics. Ionic liquids are salts that exist in the liquid phase at a temperature from about -70 ⁰C to about 300 ⁰C. The ionic liquids of the present disclosure comprise an organic cation and an organic or inorganic anion. The organic cation is typically formed by alkylation of a neutral organic species capable of holding a positive charge when a suitable anion is present.

The organic cation of the ionic liquids disclosed herein can comprise a linear, branched, or cyclic heteroalkyl unit. The term "heteroalkyl" refers to a cation as disclosed herein comprising one or more heteroatoms chosen from nitrogen, oxygen, sulfur, boron, or phosphorous capable of forming a cation. The heteroatom can be a part of a ring formed with one or more other heteroatoms, for example, pyridinyl, imidazolinyl rings, that can have substituted or unsubstituted linear or branched alkyl units attached thereto. In addition, the cation can be a single heteroatom wherein a sufficient number of substituted or unsubstituted linear or branched alkyl units are attached to the heteroatom such that a cation is formed. For example, the ionic liquid tributylmethyl phosphonium dimethyl-phosphate having the formula:

is an example of an ionic liquid wherein the heteroalkyl cation comprising linear alkyl units; three n-butyl (C₄) units and one methyl (C₁) unit. N-Ethyl-3-methyl-pyridinium ethylsulfate having the formula:

is an example of an ionic liquid comprising a cyclic heteroalkyl cation; a ring comprising 5 carbon atoms and 1 nitrogen atom. When m&re than one quaternizable heteroatom is present in a ring, only one heteroatom is alkylated.

Non-limiting examples of heterocyclic and heteroaryl units that can be alkylated to form cationic units include imidazole, pyrazoles, thiazoles, isothiazoles, azathiozoles, oxothiazoles, oxazines, oxazolines, oxazaboroles, dithiozoles, triazoles, selenozoles, oxahospholes, pyrroles, boroles, furans, thiphenes, phospholes, pentazoles, indoles, indolines, oxazoles, isothirazoles, tetrazoles, benzofurans, dibenzofurans, benzothiophenes, dibenzothoiphenes, thiadiazoles, pyrdines, pyrimidines, pyrazines, pyridazines, piperazines, piperidines, moφho lines, pyrans, annolines, phthalazines, quinazolines, and quinoxalines.

The following are examples of heterocyclic units that are suitable for forming a cyclic heteroalkyl cation unit of the disclosed ionic liquids:

pyrrolidinium piperidinium The following are further examples of heterocyclic units that are suitable for forming a cyclic heteroalkyl cation unit of the disclosed ionic liquids:

pyridinium pyridazinium pyrimidinium pyrazinium

imidazolium pyrazolium oxazolium 1,2,3-triazolium

1,2,4-triazolium

isoquinolium where each R^! and R² is, independently, a substituted or unsubstituted linear, branched, or cyclic C₁-C₆ alkyl, or substituted or unsubstituted linear, branched, or cyclic Ci-C₆ alkoxy; each R³, R⁴, R⁵, R⁶, R⁷, R⁸, and R⁹ is, independently, hydrogen, substituted or unsubstituted linear, branched, or cyclic C₁-C₆ alkyl, substituted or unsubstituted linear, branched, or cyclic C]-C₆ alkoxy, or substituted or unsubstituted linear or branched, Ci-C₆ alkoxyalkyl.

The following comprises yet another set of examples of heterocyclic units that are suitable for forming heterocyclic dication units of the disclosed ionic liquids and are referred to as such or as "geminal ionic liquids:" See Armstrong, D. W. et al., Structure and properties of high stability geminal dicationic ionic liquids, J. Amer. Chem. Soc. 2005;127(2):593-604; and Rogers, R. D. et al., Mercury(II) partitioning from aqueous solutions with a new, hydrophobic ethylene-glycol functionalized bis-imidazolium ionic -iquid, Green Chem. 2003;5:129-135 included herein by reference in its entirety.

1 , 1 '-[ 1 ,2-ethanediylbis(oxy- 1 ,2-ethanediyl)]bis[3-methy 1-lH-imidazolium- 1 -yl]

n = 3, 6, 9, 12 n = 3, 9 imidazolium and pyrrolidinium based di-cations where R¹, R⁴, R⁹, and R¹⁰ comprise a substituted or unsubstituted linear, branched, or cyclic C₁-C₆ alkyl, or substituted or unsubstituted linear, branched, or cyclic Cj-C₆ alkoxy; each R⁵, R⁶, R⁷, and R⁸ is, independently, hydrogen, substituted or unsubstituted linear, branched, or cyclic Ci-C₆ alkyl, substituted or unsubstituted linear, branched, or cyclic C₁-C₆ alkoxy, or substituted or unsubstituted linear or branched, Ci-C₆ alkoxyalkyl.

The anionic portion of the ionic liquid can comprise an inorganic or organic moiety. Non-limiting examples of anions include inorganic anions: halogens, (i.e., F, Cl, Br, and I); borides, BX₄, wherein X represents halogen, (i.e., BF₄, BCl₄), and the like; phosphates(V), PX₆; PF₆, and the like; arsenate(V), AsX₆; AsF₆, and the like; stibate(V) (antimony), SbX₆; SbF₆, and the like; CO₃ ²; NO₂, NO₃, SO₄ ², and (CF₃)SO₃.

Other non-limiting examples of ionic liquid anions include substituted azolates, that is, five membered heterocyclic aromatic rings that have nitrogen atoms in either positions 1 and 3 (imidazolates); 1, 2, and 3 (1,2,3-triazolates); or 1, 2, 4 (1, 2, 4-triazolate).

Substitutions to the ring occur at positions that are not located in nitrogen positions (these are carbon positions) and include CN (cyano), NO₂ (nitro), and NH₂ (amino) group appended to the heterocyclic azolate core.

Further non- limiting examples of anions include substituted or unsubstituted borides: B(R¹⁰)₄; substituted or unsubstituted sulfates: (R¹⁰O)S(^O)₂O; substituted or unsubstituted acyl units R¹ CO₂, for example, acetate CH₃CO₂, proprionate, CH₃CH₂CO₂, butyrate CH₃CH₂CH₂CO₂, and benzylate, C₆H₅CO₂; substituted or unsubstituted phosphates: (R¹⁰O)₂P(O)O; substituted or unsubstituted carboxylates: (R¹⁰O)C(O)O; substituted or unsubstituted azolates wherein the azolate can be substituted on a carbon atom by a unit chosen from cyano, nitro, and amino. Non-limiting examples of R¹⁰ include hydrogen; substituted or unsubstituted linear branched, and cyclic alkyl; substituted or unsubstituted linear, branched, and cyclic alkoxy; substituted or unsubstituted aryl; substituted or unsubstituted aryloxy; substituted or unsubstituted heterocyclic; substituted or unsubstituted heteroaryJ; acyl; silyl; boryl; phosphino; amino; thio; and seleno. One embodiment of ionic liquids comprise an anion chosen from Cl, Br, I, (CF₃)SO₃, (R¹⁰O)SC-O)₂O; (R^I0O)₂P(=O)O; (R¹⁰O)C(O)O; and R¹⁰CO₂; each R¹⁰ is independently C]-C₄ alkyl. Anions that are chosen from Cl, Br, I, and R¹⁰CO₂ have been found to be convenient in forming the compositions of step (a) in the compositions and processes disclosed herein.

The following is a description of the short hand method used throughout the specification for referring to the imidazolium-based ionic liquids disclosed herein. The template:

[C_nmim] represents the cation portion of the ionic liquid wherein C_n represent an alkyl or substituted alkyl moiety having n number of carbon atoms. The term "mim" refers to "methyl substituted imidazolium." Referring to the generic imidazolium formula:

wherein R³, R⁴, and R³ are each hydrogen, can also be written as follows:

wherein either nitrogen can be depicted as having a positive charge. By the convention used herein the methyl group of "mim" refers to the R¹ moiety and the C₁, substituent is the R² moiety. Therefore [C₄min] represents a cation having the formula:

H₃C^_N^®-C₄H₉

which can be equally well represented by the formula:

H -C₄ 4H^π9

\v±>y

The anion portion of the ionic liquid is written without the charge, for example, Cl and PF₆.

The following are non-limiting examples of ionic liquids written in the short hand convention with the corresponding formula: i) [C₄mim]Cl having the formula: c.^Θ

ii) [C₂mim] (C₂H₅O)SO₃ having the formula:

V Θ

<-2^H5 O

iii) [C₄HiIm]Cl having the formula: ci^θ

iv) [C₂mim]Cl having the formula:

v) [C₂mim] (C₂H₅O)₂PO₂ having the formula:

vi) [C₄mim]BF4 having the formula:

vii) [C₄mim]PF₆ having the formula:

In one embodiment, the electrolytic cell comprises an ionic liquid wherein the anion of the ionic liquid is chloride ion. In another embodiment, the ionic liquid comprises a cation having the formula: R¹ ^^ R² wherein R¹ and R² are each independently methyl, ethyl, n-propyl, iso-propyl, n- butyl, wo-butyl, n-pentyl, or n-hexyl. Non-limiting examples of cations include l-methyl-3- methylimidazolium, l-methyl-3-ethylimidazolium, l-methyl-3-propylimidazolium, 1- methyl-3-butylimidazolium, l-methyl-3-pentylimidazolium, l-methyl-3-hexylimidazolium, l-ethyl-3-methylimidazolium, l-ethyl-3-ethylimidazolium, l-ethyl-3-propylimidazolium, 1- ethyl-3-butylimidazolium, l-ethyl-3-pentylimidazolium, l-ethyl-3-hexylimidazolium, 1- propyl-3-methylimidazolium, l-propyl-3-ethylimidazolium, l-propyl-3-propylimidazolium, 1 -propyl-3-butylimidazolium, 1 -propyl-3-pentylimidazolium, 1 -propyl-3-hexylimidazolium, l-butyl-3-methylimidazolium, l-butyl-3-ethylimidazolium, l-butyl-3-propylimidazolium, 1 -butyl-3-butylimidazolium, 1 -butyl-3-pentylimidazolium, 1 -butyl-3-hexylimidazolium, and l-hexyl-3-methylimidazolium.

Non-limiting examples of ionic liquids suitable for use in the disclosed electrolytic ceils include l-methyl-3-methylimidazolium chloride, l-methyl-3-ethylimidazolium chloride, l-methyl-3-propylimidazolium chloride, 1 -methyl-3-butylimidazolium chloride, 1- methyl-3-pentylimidazolium chloride, l-methyl-3-hexyl-imidazolium chloride, l-ethyl-3- methylimidazolium chloride, l-ethyl-3-ethylimidazolium chloride, l-ethyl-3- propylimidazolium chloride, l-ethyl-3-butylimidazolium chloride, l -ethyl-3- pentylimidazolium chloride, l-ethyl-3-hexylimidazolium chloride, l-propyl-3-methyl- imjdazolium chloride, l-propyl-3-ethylimidazolium chloride, l-propyl-3- propylimidazolium chloride, 1 -propyl-3-butylimidazolium chloride, l-propyl-3- pentylimidazolium chloride, 1 -propyl-3-hexylimidazolium chloride, l-butyl-3- lnethylimidazolium chloride, l-butyl-3-ethyl-imidazolium chloride, l-butyl-3- propylimidazolium chloride, 1 -butyl-3-butylimidazolium chloride, l-butyl-3- pentylimidazolium chloride, 1 -butyl-3-hexylimidazolium chloride, and l-hexyl-3- rπethylimidazolium chloride.

The following examples are set forth below to illustrate the methods and results according to the disclosed subject matter. These examples are not intended to be inclusive of all aspects of the subject matter disclosed herein, but rather to illustrate representative methods and results. These examples are not intended to exclude equivalents and variations of the present invention, which are apparent to one skilled in the art.

Efforts have been made to ensure accuracy with respect to numbers (e.g., amounts, temperature, etc.) but some errors and deviations should be accounted for. Unless indicated otherwise, parts are parts by weight, temperature is in ⁰C or is at ambient temperature, and pressure is at or near atmospheric. There are numerous variations and combinations of reaction conditions, e.g., component concentrations, temperatures, pressures and other reaction ranges and conditions that can be used to optimize the product purity and yield obtained from the described process. Only reasonable and routine experimentation will be required to optimize such process conditions.

EXAMPLE 2 Underivitized microcrystalline cellulose (Aldrich Chemical Co.; Milwaukee, WI), was dissolved in the IL, l-butyl-3-methylimidazolium chloride ([C₄TmInJCl) to form a 5 weight percent (wt.%) solution using microwave pulse heating as previously described (PCT Publication No. WO03/029329 A2; Swatloski et al., JAm Chem Soc 2002, 124:4974- 4975; Swatloski et at., "Ionic Liquids for the Dissolution and Regeneration of Cellulose" In Moiten Salts XIII: Prøceedings-of the International Symposium, Trulove et al., Eds., The Electrochemical Society: Pennington, NJ, 2002; Vol. 2002-19, pp. 155-164). After- complete dissolution at around 120 to 150 °C, forming a viscous clear solution, the mixture was allowed to cool to approximately 60⁰C, forming a super-cooled liquid. The substrate prepared according to Example 1 is then added to the cellulose solution at a concentration of approximately 20 wt.% relative to the cellulose component and the mixture was manually homogenized (to ensure complete mutual dispersion) and then cast as a film (1 mm thickness) on a glass plate using coating rods (R&D Specialties, Weber. NY). The films were reconstituted and the IL solvent was leached from the films with deionized (DI) H₂O. Following complete reconstitution, films were placed in a bath and immersed in DI H₂O for at least 24 hours (h) to leach residual [C₄mim]Cl from the film. Other advantages which are obvious and which are inherent to the invention will be evident to one skilled in the art. It will be understood that certain features and sub- combinations are of utility and may be employed without reference to other features and sub-combinations. This is contemplated by and is within the scope of the claims. Since many possible embodiments may be made of the invention without departing from the scope thereof, it is to be understood that all matter herein set forth or shown in the accompanying drawings is to be interpreted as illustrative and not in a limiting sense.

Claims

WHAT IS CLAIMED IS:

1. A composite, comprising, an active substrate having the formula chosen from: i)

ϋ)

_L!-[ZA]_S

I R-N

[ZA]₅. iii)

^{• ■} R-O-L^[ZA]_S j ₀₁. iv)

RS-O-[ZA]₁₁. wherein R is an anchoring unit chosen from: i) hydrogen; ii) C₁-Cj₂ linear, branched, or cyclic alkyl; iii) C₆ or Cio aryl; and iv) C₇-Ci₂ alkylenearyl; each L unit is independently chosen from: i) -(CR^laR^lb)_w-; and ii) -(CR^2aR^2b)_x[X(CR^3aR^3b)_y]_zX-; the index w is from 1 to 50_.. the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20;

R^Ia and R^lb are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl;

R^2a, R^2b, R^3a, and R^3b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; iii) -(CR^5aR^5b)_jOH; and iv) -[(CR^6aR^6b)_kNH₂; R^5a, R^5b, R^6a, and R^6b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; the indices j and k are each independently from 2 to 20; each X is independently chosen from i) -O-; ii) -NR⁷-; iii) -S-; iv) -C(O)-; v) -NHC(O)-; vi) -C(O)NH-; vii) -OC(O)-; and viii) -C(O)O-;

R⁷ is a ZA unit, a second bond to a~ZA unit which serves to act together with the other bond to form a double bond, hydrogen, C₁-C₄ alkyl, or a unit having the formula -[(CR^8aR^8b)_mNH]_n(CR^9aR^9b)_pNH₂;

R^8a, R^8b, R^9a, and R^9b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; ihe index m is from 2 to 20; the index n is from O to 6; the index p is from 2 to 20; each Z unit is independently a biohydrolyzable linking group; each A unit is independently a component of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released; and the index s is 1 or 2.

2. A composite according to Claim 1, comprising: a) a regenerated cellulose, pectin, chitin or starch matrix; and b) an active substrate having the formula chosen from: i)

[ZA]₅ ϋ)

,_^ -[ZA]₅

R-N

I

[ZA]₅. iii)

iv)

R-S-L^[ZA]₅. wherein R is an anchoring unit chosen from: i) hydrogen; ii) C₁-Cj₂ linear, branched, or cyclic alkyl; iii) C₆ or C₁₀ aryl; and iv) C₇-C₁₂ alkylenearyl; each L unit is independently chosen from: i) -(CR^laR^lb)w-; and ii) -(CR^2aR^2b)χ[X(CR^3aR^3b)_y]_zX-; the index w is from 1 to 50, the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20;

R^la and R^lb are each independently chosen from: i) hydrogen; and ii) C-C₂ alkyl;

R^2a, R^2b, R^3a, and R^3b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; iii) -(CR^5aR^5b)_jOH; and iv) -[(CR^6aR^6b)_kNH₂;

R^5a, R^5b, R^6a, and R^6b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; the indices j and k are each independently from 2 to 20; each X is independently chosen from i) -O-; ii) -NR⁷-; iii) -S-; iv) -C(O)-; v) -NHC(O)-; vi) -C(O)NH-; vii) -OC(O)-; and viii) -C(O)O-;

R⁷ is a ZA unit, a second bond to a ZA unit which serves to act together with the other bond to form a double bond, hydrogen, Ci -C₄ alkyl, or a unit having the formula -[(CR^8aR^8b)_mNH]_n(CR^9aR^9b)_pNH₂;

R^8a, R^8b, R^9a, and R^9b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; the index m is from 2 to 20; the index n is from O to 6; the index p is from 2 to 20; each Z unit is independently a biohydrolyzable linking group; each A unit is independently a component of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released; and the index s is 1 or 2.

3. The composite according to either Claim 1 or 2, wherein R is hydrogen.

4. The composite according to either Claim 1 or 2, wherein R is phenyl or benzyl.

5. The composite according to either Claim 1 or 2, wherein R is ethyl.

6. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-(CH₂V wherein the index w is from 2 to 20.

7. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-[CH₂CH(CH₃)]_W- or -[CH(CH₃)CH₂]*- wherein the index w is from 2 to 20.

8. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-(CH₂)_x[O(CH₂)_y]_zO- wherein the index x is from 1 to 6, the index y is from 2 to 6, and the index z is from 2 to 12.

9. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-(CH₂)_X[O(CH₂CH(CH₃))]₂O- or -(CH₂)_X[O(CH(CH₃)CH₂)]_ZO- wherein the index x is from 1 to 6, and the index z is from 2 to 12.

LO. The composite according to either Claim 1 or 2, Wherein, L¹, L², and L³ eaclvhave the formula:

-<CH₂)_X[O(CH₂CH(CH₃))]_ZN- or -(CH₂)_X[O(CH(CH₃)CH₂)]_ZN- wherein the index x is from 1 to 6, and the index z is from 2 to 12.

11. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-(CH₂)_X[NR⁷(CH₂CH₂)]_Z-; wherein R⁷ has the formula:

-[CH₂CH₂NH]_nCH₂CH₂NH₂; wherein the index n is from 0 to 6.

12. The composite according to either Claim 1 or 2, wherein L¹, L², and L³ each have the formula:

-[NHC(O)CH[(CH₂)₄NH₂)]_zNH-; v/herein the index z is from 1 to 10.

13. The composite according to either Claim 1 or 2, wherein each Z- A is independently chosen from: i) -(CR^I0aR^10b)_qC(O)-A; ii) -C(O)(CR^10aR^10b)_qC(O)-A; iii) -(CR^10aR^10b)_qC(O)O-A; iv) -OC(OXCR^10aR^I0b)_qC(O)O-A;

V) -(CR^1OaR^1Ob)_qNH-A;

Vi) -NH(CR^10aR^10b)_qC(O)-A; vii) -(CR^10aR^10b)_qC(O)NH-A; viii) -NHOC(O)(CR^I0aR^10b)_qC(O)O-A; ix)

x)

xii)

R^1Oa and R^1Ob are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; and the index q is from O to 10.

14. A composite according to either Claim 1 or 2, wherein the substrate has the formula:

R^1Oa and R^1Ob are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; and the index q is from O to 10; and the index q is from O to 10; the index s is 1 or 2; the indices z¹ + z² + z³ = z.

15. The composite according to either Claim 1 or 2, wherein the index x = 1; and the indices z' + z² + z³ = z; z is from 5 to 6.

16. The composite according to either Claim 1 or 2, wherein the substrate has the formula:

the indices z¹ + z² + z³ = z..

17. The composite according to either Claim 1 or 2, wherein the index x = 1 ; and the indices z¹ + z² + z³ = z, z is from 5 to 6.

18. The composite according to either Claim 1 or 2, wherein the index x = 1; and the indices z¹ + z² + z³ = z, z is from 50 to 100.

19. The composite according to either Claim 1 or 2, wherein the substrate releases a physiologically active compound having the formula: H wherein A is chosen from: i) C)-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C_2O substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted C₁-C₂₀ heterocyclic; and vii) substituted or unsubstituted C₁-C_2O heteroaryl.

20. The composite according to either Claim 1 or 2, wherein the substrate releases a physiologically active compound having the formula:

wherein A is chosen from: i) Ci-C_2O substituted or unsubstituted, linear, branched or cyclic alkyi; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C_2O substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂O alkylenearyl; vi) substituted or unsubstituted Ci-C_2O heterocyclic; and vii) substituted or unsubstituted Ci-C₂₀ heteroaryl.

21. The composite according to either Claim 1 or 2, wherein the substrate releases a physiologically active compound having the formula:

HO-A wherein A is chosen from: i) Ci-C_2O substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted C₁-C₂₀ heterocyclic; and vji) substituted or unsubstituted C₁-C₂₀ heteroaryl.

22. The composite according to either Claim 1 or 2, wherein the substrate releases a fragrance raw material.

23. The composite according to either Claim 1 or 2, wherein the substrate has the formula:

wherein each R³⁰ is independently chosen from: i) C₁-Cj₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl: iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted C₁-C₂₀ heterocyclic; and vii) substituted or unsubstituted C₁-C₂₀ heteroaryl.

24. The composite according to either Claim 1 or 2, wherein the substrate releases a compound chosen from Phenoxymethylpenicillin potassium (Veetids); Oxacillin sodium (Bactocill); Benzylpenicillin potassium (Pfizerpen); Phenethicillin potassium (Syncillin); Flucloxacillin sodium (Floxapen); Propicillin potassium; Benzylpenicillin benzathine hydrate (Bicillin L-A); Meticillin sodium (Staphcillin); Hetacillin potassium (Hetacin-K); Phenoxymethylpenicillin benzathine; Clindamycin phosphate (Cleocin); Clindamycin palmitate hydrochloride (Cleocin pediatric); Clindamycin hydrochloride (Cleocin hydrochloride); Lincomycin hydrochloride (Lincocin); Vancomycin (Vancoled); Quinupristin; Dalfopristin; Quinupristin - dalfopristin mixt; (Synercid); Novobiocin sodium (Albamycin); Arbekacin sulfate (Habekacin);Teicoplanin (Tagocid); and Mupirocin calcium hydrate (Bactroban); Carindacillin sodium (Geocillin); Pivmecillinam hydrochloride (Melysin); Carfecillin sodium; Aztreonam (Azactam); Carumonam sodium (Amasulin); Tobramycin (Tobracin); Amikacin sulfate (Amikin); Kanamycin monosulfate (Kantrex); Paromomycin sulfate (Humatin); Isepamicin sulfate (Isepacin); Spectinomycin hydrochloride (Trobicin); Colistin sodium methanesulfonate (Coly-Mycin M); Polymixin B sulfate (Aerosporin); and Ceftibuten (Cedax); Anhydrous ampicillin (Omnipe); Amoxicillin hydrate (Amoxil); Piperacillin sodium (Pentcilli); Bacampicillin hydrochloride (Spectrobid); Ampicillin hydrate (Amcill); Ciclacillin (Cyclapen-W); Sultamicillin tosilate (Unasy); Lenampicillin hydrochloride (Valacilli); Ampicillin sodium (Omnipen); Carbenicillin sodium (Geope); Talampicillin hydrochloride (Aseocilli); Mezlocillin sodium. (Mezli); Ticarcillin sodium (Ticar); Aspoxicillin (Doyle); Cefaclor (Alenfral); Cefadroxil (Sumacef); Cefixime (Suprax); Cefotetan; Cefalexin (Keflex); Cefradine (Anspor); Cefazolin sodium (Ancef); Cefalotin sodium (Kefli);Cefapirin sodium (Cefadyl); Cefmetazole sodium (Zefazone); Cefoxitin sodium (Mefoxi); Cefuroxime axetil (Cefti); Cefuroxime sodium (Zinacef); Cefdinir; (Cefzo);Cefoperazone sodium (Cefobid); Cefotaxime sodium (Clafora); Cefpodoxime proxetil (Vanti); Ceftazidime (Fortaz); Ceftizoxime sodium (Cefizox); Ceftriaxone sodium (Rocephi); Cefluprenam N); Cefaloridine (Kefloridi); Cefepime dihydrochloride (Maxipime); Cefacetrile sodium (Celtol); Cefpirome sulfate (Cefrom); Cefotiam hexetil hydrochloride (Pansporin-T); Ceftezole sodium (Celosli); Cefpimizole sodium AAjicef); Cefditoren pivoxil (Meiact); Cefetamet pivoxil hydrochloride (Cefyl); Cefcapene pivoxil hydrochloride hydrate (Flomox); Cefovecin sodium; Cefteram pivoxil (Tomiro); Cefuzonam sodium; Cefbuperazone sodium (Keiperazo); Cefotiam hydrochloride (Cerado); Cefodizime sodium (Kenicef); Cefpiramide sodium A(Suncefal); Cefminox sodium (Meiceli); Cefaloglycin; Cefmatilen hydrochloride hydrate; Cefsulodin sodium (Takesuli); Cefamandole sodium (Kefdole); Cefazolin sodium hydrate; Cefotetan sodium (Cefota); Cefoselis sulfate (Winsef); Cefozopran hydrochloride (Firstci); Propylene glycolate cefatrizine (Seapuro); Cefroxadine (Oraspor); Flomox ef sodium (Flumari); Latamoxef sodium (Moxam); Netilmicin sulfate (Netromyci); Gentamicin sulfate (Garamyci); Dibekacin sulfate (Panimyci); Micronomicin sulfate (Sagamici); ekanamycin sulfate (Kanendomyci); Astromicin sulfate (Fortimici); Sisomicin sulfate (Sisepti); Ribostamycin sulfate Vistamyci); Fosfomycin calcium Fosmici); Fosfomycin sodium (Fosmicin S); Imipenem hydrate; Amoxicillin - potassium clavulanate combination; (Clavamox); Imipenem hydrate - cilastatin sodium (Primaxi); Piperacillin sodium (Pentcilli); Tazobactam; Panipenem; Biapenem (Omegaci); Doripenem hydrate; Faropenem sodium (Farom); Ampicillin sodium (Omnipen); Cilastatin sodium; Meropenem trihydrate (Merrem); Sulbactam sodium; Piperacillin hydrate; Clavulanate potassium; Piperacillin-tazobactam combination (Tazoci); and Panipenem-betamipron (Carbeni).

25. The composite according to either Claim 1 or 2, wherein the substrate releases a fragrance raw material chosen from: methyl, 2,4-dimethyl-3-cyclohexεne-l -methyl, 2,4-dimethyl cyclohexane methyl, 5,6-dimethyl-l-methylethenyl-bicyclo[2.2.1]hept- 5-ene-2 -methyl, 2,4,6-trimethyl-3-cyclohexene-l -methyl, 4-(l- 1 methyletnyijcyclohexylmethyl, α-3,3-trimethyl-2-norboranylmethyl, 1,1-dimethyl- l-(4-methylcyclohex-3-enyl)methyl, ethyl, 2-phenylethyl, 2-cyclohexylethyl, 2-(o- methylphenyl)ethyl, 2-(m-methylphenyl)ethyl, 2-(p-methylphenyl)ethyl, 6,6- dimethylbicyclo[3.1.1 ]hept-2-ene-2-ethyl, 2-(4-methylphenoxy)ethyl, 3,3-dimethyl- A²-β-norbornanylethyl, 2-methyl-2-cyclohexylethyl, 1 - (4-isopropylcyclohexyl)ethyl, I -phenyl- 1 -hydroxyethyl, 1 , 1 -dimethyl-2-phenylethyl, 1 , 1 -dimethyl-2-(4- methylphenyl)ethyl, propyl, 1-phenylpropyl, 3-phenylpropyl, 2-phenylpropyl, 2- (cyclododecyl)-propan-l-yl, 2,2-dimethyl-3-(3-methylphenyl)propan-l -yl, 2-methyl- 3-phenylpropyl, 3-phenyl-2-propen-l-yl, 2-methyl-3-phenyl-2-propen-l-yl, α-n- pentyl-3-phenyl-2-propen-l-yl, ethyl-3-hydroxy-3-phenyl propionate, 2-(4- methylphenyl)-2-propyl, butyl, 3-methylbutyl, 3-(4-methylcyclohex-3-ene)butyl, 2- methyl-4-(2,2,3-trimethyϊ-3-cyclopenten-l-yl)butyl, 2-ethyl-4-(2,2,3- trimethylcyclopent-3-enyl)-2-buten-l-yl, 3-methyl-2-buten-l-yl, 2-methyl-4-(2,2,3- trimethyl-3-cyclopenten-l-yl)-2-buten-l-yl, 3-hydroxy-2-butanone, ethyl 3- hydroxybutyrate, 4-phenyl-3-buten-2-yl, 2-methyl-4-phenylbutan-2-yl, 4-(4- hydroxyphenyl)butan-2-one, 4-(4-hydroxy-3-methoxyphenyl)butan-2-one, pentyl, cis-3-pentenyl, 3-methylpentyl, 3-methyl-3-penten-l-yl, 2-methyl-4-phenylpentyl, 3-methyl-5-phenylpentyl, 2-methyl-5-phenylpentyl, 2-methyl-5-(2,3- dimethyltricyclo-[2.2.1.0(2,6)]hept-3-yl)-2-penten-l-yl, 4-methyl-l -phenyl-2-pentyl, (1 -methyl-bicyclo [2.1.1 ]hepten-2-yl)-2-methylpent- 1 -en-3-yl, 3-methyl- 1 - phenylpent-3-yl, 1 ,2-dimethyl-3-(l -methylethenyl)cyclopent- 1 -yl, 2-isopropyl-4- methyl-2-hexenyl, cis-3-hexen-l-yl, trans-2-hexen-l-yl, 2-isopropenyl-5-methyl-4- hexen-1-yl, 2-ethyl-2-prenyl-3-hexenyl, 2-ethylhexyl, l-hydroxymethyl-4- isopropenyl- 1 -cyclohexenyl, 1 -methyM-isopropenylcyclohex-ό-en^-yl, 6-methyl- 3-isopropenylcyclohex- 1 -yl, 1 -methyl-4-isopropenylcyclohex-3-yl, 4-iso-propyl- 1 - methylcyclohex-3-yl, 4-tert-butylcyclohexyl, 2-tert-butylcyclohexyl, 2-tert-butyl-4- methylcyclohexyl, 4-isopropylcyclohexyl, 4-methyl-l-(l-methylethyl)-3- cyclohexen- 1 -yl, 2-(5,6,6-trimethyl-2-norbomyl)cyclohexyl, isobomylcyclohexyl, 3,3,5-trimethylcyclohexyl, 1 -methyl-4-isopropylcyclohex-3-yl, 1 ,2-dimethyl-3-(l - methylethyl)-cyclohexan-l-yl, heptyl, 2,4-dimethylhept-l-yl, 2,4-dimethyl-2,6- heptandienyl, 6,6-dimethyl-2-oxymethylbicyclo[3.1.1 ]hept-2-en- 1 -yl, 4-methyl-2,4- heptadien-1-yl, 3,4,5,6,6-pentamethyl-2-heptyl, 3,6-dimethyl-3-vinyl-5-hepten-2-yl, 6,6-dimethyl-3-hydroxy-2-methylenebicyclo[3.1.1]heptyl, 1,7,7-trimethylbicyclo- [2.2.1]hept-2-yl, 2,6-dimethylhept-2-yl, 2,6,6-trimethylbicyclo[1.3.3]hept-2-yl, octyl, 2-octenyl, 2-methyloctan-2-yl, 2-methyl-6-methylene-7-octen-2-yl^7- methyloctan-1-yl, 3,7-dimethyl-6-octenyl, 3,7-dimethyl-7-octenyl, 3,7-dimethyl-6- octen-1-yl, 3,7-dimethyl-2,6-octadien-l-yl, 3,7-dimethyl-2,6-octadien-l-yl, 3,7- dimethyl-l,6-octadien-3-yl, 3,7-dimethyloctan-l-yl, 3,7-dimethyloctan-3-yl, 2,4- octadien-1-yl, 3,7-dimethyl-6-octen-3-yl_; 2,6-dimethyl-7-octen-2-yl, 2,6-dimethyl- 5,7-octadien-2-yl, 4,7-dimethyl-4-vinyl-6-octen-3-yl, 3-methyloctan-3-yl, 2,6- dimethyloctan-2-yl, 2,6-dimethyloctan-3-yh 3,6-dimethyloctan-3-yl, 2,6-dimethyl-7- octen-2-yl, 2,6-dimethyl-3,5-octadien-2-yl, 3-methyl-l-octen-3-yl, 7-hydroxy-3,7- dimethyloctanalyl, 3-nonyl, 6,8-dimethylnonan-2-yl, 3-(hydroxymethyl)-2- nonanone, 2-nonen-l-yl, 2,4-nonadien-l-yl, 2,6-nonadien-l-yl, cis-6-nonen-l-yl, 3,7-dimethyl-l,6-nonadien-3-yl, decyl, 9-decenyl, 2-benzyl-M-dioxa-5-yl, 2-decen- 1 -yl, 2,4-decadien-l-yl, 4-methyl-3-decen-5-yl, 3,7,9-trimethyl-l,6-decadien-3-yl, undecyl, 2-undecen-l-yl, 10-undecen-l-yl, 2-dodecen-l-yl, 2,4-dodecadien-l-yl, 2,7,1 l-trimethyl-2,6,10-dodecatrien-l-yl, 3,7,1 l-trimethyl-l,6,10,-dodecatrien-3-yl, 3,7,1 l,15-tetramethylhexadec-2-en-l-yl, 3,7,1 l,15-tetramethylhexadec-l-en-3-yl, benzyl, p-methoxybenzyl, para-cymen-7-yl, 4-methylbenzyl, 3,4- methylenedioxybenzyl, 2-(methyl)carboxy- 1 -hydroxyphenyl, 2-(benzyl)carboxy- 1 - hydroxyphenyl, 2-(cis-3-hexenyl)-carboxy- 1 -hydroxyphenyl, 2-(n-pentyl)carboxy- 1 - hydroxyphenyl, 2-(2-phenylethyl)carboxy- 1 -hydroxyphenyl, 2-(n-hexyl)carboxy- 1 - hydroxyphenyl, 2-methyl-5-isopropyl- 1 -hydroxyphenyl, 4-ethyl-2-methoxyphenyl, 4-allyl-2-methoxy- 1 -hydroxyphenyl, 2-methoxy-4-( 1 -propenyl)- 1 -hydroxyphenyl, 4-allyl-2,6-dimethoxy- 1 -hydroxyphenyl, 4-tert-butyl- 1 -hydroxyphenyl, 2-ethoxy-4- methyl- 1 -hydroxyphenyl, 2-methyl-4-vinyl- 1 -hydroxyphenyl, 2-isopropyl-5-methyl- 1 -hydroxyphenyl, 2-(isopentyl)-carboxy- 1 -hydroxyphenyl, 2-(ethyl)carboxy- 1 - hydroxyphenyl, 6-(methyl)carboxy-2,5-dimethyl-l ,3-dihydroxyphenyl, 5-methoxy- 3-methyl- 1 -hydroxyphenyl, 2-tert-butyl-4-methyl- 1 -hydroxyphenyl, 1 -ethoxy-2- hydroxy-4-propenylphenyl, 4-methyl-l -hydroxyphenyl, 4-hydroxy-3- methoxybenzaldehyde, 2-ethoxy-4-hydroxybenzaldehyde, decahydro-2-naphthyl, 2,5,5-trimethyl-octahydro-2-naphthyl, 1 ,3,3-trimethyl-2-norbomyl, 3a,4,5,6,7,7a- hexahydro-2,4-dimethyl-4,7-methano-lH-inden-5-yl, 3a,4,5,6,7,7a-hexahydro-3,4- dimethyl-4,7-methano- l//-inden-5-yl, 2-methyl-2-vinyl-5-(l-hydroxy- 1 - methylethyl)tetrahydrofuranyl, and β-caryophyllenyl.

26. The composite according to either Claim 1 or 2, wherein the substrate releases a compound chosen from: acetoin (acetyl methyl carboriol), agaric acid, α-roi-one, amyl butyrate, benzaldehyde, 3,4-benzopyren, β-azarone, β-ionone, carvomeiithenol, cinnamaldehyde, coumarin, ethyl acetate, ethyl butyrate, ethyl lactate, ethyl propionate, heliotropine, hydrocuanic acid, hypercin, methyl cyclopentenolone, methyl nonyl ketone, pulegone, quassine, quinine, safrole, spartein, thujone, and vanillin.

27. The composite according to either Claim 1 or 2, wherein the substrate releases a compound chosen from simvastatin, salmeterol xinafoate, fluticasone propionate, rofecoxib, peginterferon, conjugated estrogenic hormones, ondansetron hydrochloride* fluticasone propionate, conepezil hydrochloride, paclitaxel, sodium risedronate, bicalutamide, irbesartan, ipratropium bromide Albuterol (salbutamol), meloxicam, Lamivudine, Zidovudine, abacavir sulphate, levothyroxine, finasteride, fenofibrate, budesonide, formoterol fumarate, tolterodine tartarate, mometasone furoate, ipratropium bromide, orlistat, propofol, potassium losartan, salbutamol sulphate, and stavudine.

28. The composite according to either Claim 1 or 2, wherein the substrate releases a compound chosen from: cc, α-dimethylphenethyl acetate, α, α-dimethylphenethyl butyrate, α, α-dimethylphenethyl formate, 3-methyl-4-phenyl-3-butene-2-one, 4- emthyl-l-phenyl-2-pentanone, α-ethylbenzyl butyrate, isoeugenyl benzylether, α- isomethylionone, β-isomethylionone, α-methyl cinnamaldehyde, α-methyl ionone, β-methyl ionone, α-methyl lactate, α-methylbenzyl butyrate, α-methylbenzyl formate, α-methylbenzyl isobutyrate, α-methylbenzyl propionate, β-naptyl anthranilate, β-naptyl ethylether, β-naptyl isobutyl ether, α-terpinyl anthranilate, o- (ethoxymethyl) phenol, l-(p-methoxyphenyl)-l-penten-3-one, 1, 4-nonanediol diacetate, 1, 9-nonanedithiol, l,2,3-tris(rethocy)-ethoxy-propane, 1 ,2-butanedi thiol, l,2-di(l'-ethoxyl) propane, 1,2-propanedithiol, 1,3-butanedithiol, 1,8-octanedithiol, 10-undecen-l-yl acetate, 10-undecenal, 1-ethylhexyl tiglate, 1 -phenyl -2 -propyl butyrate, l-phenyl-3 or 5-propylpyrazole, 2-(l-methylpropyl) thiazole, 2-(2-butyl)-4, 5-dimethyl-3-thiazoline, 2-(3-phenylpropyl) pyridine, 2-(3-phenylpropyl), tetrahydrofuran, 2-(p-tolyl)-propanal, 2, 6-nonadienal diethyl acetal, 2,3 or 10- mercaptopinane, 2,3-butanedithiol, 2,4-dimethyl-2-pentenoic acid, 2,4-dimethyl-5- acetylthj.iizole, 2,5-dimethyl-2, 5-dihydroxy-l, 4-dithiane, 2,5-dimethyl-3-furanthiol, 2,5-dimethyl-3-thioisovaleryfuran, 2,5-dimetyl -3-thoruroylfuran, 2,6,6-trimethyl-l- cyclohexen- 1 acetaldehyde, 2,6-dimethyl-3-(2-methyl-3-furyl) thio-4-heptanone, 2,6dimethyl-4-heptanol, 2,6-dimethyl-6-hepten-l-ol, 2,6-dimethyloctanal, 2-2- dithiodithiophene, 2-amyl-5 or keto- 1 , 4-dioxane, 2-benzofuran carbozaldehyde, 2- butyl-2-butenal, 2-butyl-5 or 6-keto-l, 4-dioxane, 2-ethocythiazole, 2-ethyl-l, 3, 3- rrimethyl-2-norbornanol, 2-ethyl-2-heptanal, 2-ethylbutyl acetate, 2-ethylthiophenol, 2-furan-methanethiol formate, 2-hexylidene cyclopentanone, 2-hydroxy-2- cyclohexen-1-one, 2-hydroxy-3, 5,5-trimethyl-2-cyclohexenone, 2-hydroxymethyl- 6, 6-dimethyl-bioyclo (3,1,1) hept-2-enyl formate, 2-mercaptopropionic acid, 2- methoxy-5 or 6-isopropylpyrazine, 2-methyl 2-oxo-3-methylpentanoate, 2-methyl-3, 5 or 6-metnylthio-pyrazine, 2-methyl-3,5 or 6-furfurylthio-pyrazine, 2-methyl-3- ήiranthiol, 2-methyl-3-tolyl-propanal, 2-methyl-4-pentenoic acid, 2-methyl-4- phenyl-2-butanol, 2-methyl-4-pheylbutanal, 2-methyl-5-methoxythiazole, 2- methylallyl butyrate, 2-methyloctanl, 2-methylundecanal, 2-pentyl-l-butan-3-one, 2- phenyl-1-propanol, 2-phenyl-3-(2-furyl)-prop-2-enal, 2-phenyl-3-carbethoxy furan, 2-phenyl-4-pentenal, 2-phenylpropanal, dimethyl acetal, 2-phenylpropionaldehyde, 2-phenylpropyl butyrate, 2-phenylpropyl isobutyrate, 2-pyridine methanethiol, 2- seo-butylcyclohexanone, 2-thienyhnercaptan, 2-trans-6-trans-octadienal, 3-((2- mercapto- 1 -methylpropyl)thio)-2-butanol, 3-((2-methyl-3-furyl)-thio)-4-heptanone, 3-(2-methylpropyl) pyridine, 3-(5-metrhyl-2-furyl) butanal, 3-(hydroxymethyl)-2- heptanone, 3-(hydroxymethyl)-2-octanone, 3-(methylthio) butanal, 3-(p-isopropyl)- phenyl propanal, 3,5,5-trimethylhexanal, 3,5,5-trimethylhexanol, 3.7-dimethyl-2, 6- oxtadienyl 2-ethylbutyrate, 3-acetyl-2, 5-dimethylfuran, 3-acetyl-2,5- dimethylthiophene, 3-benzyl-4-heptanone, 3-ethyl-2-hydroxy-4-methyl-cyclopent-2- en-l-one, 3-heptyl-5-methyl-2(3H)-furanone, 3-mercapto-2-butanol, 3-mercapto-2- butanone, 3-mercapto-2-pentanone, 3-methyl-2-phenylbutanal, 3-methyl-5-propyl-2- cyclohexene-1-one, 3-octen-2-ol, 3-oxobutanal dimethyl acetal, 3-phenyl-4- pentenal, 3-phenylpropyl formate, 3-phenylpropyl hexanoate, 3-phenylpropyl isobutyrate, 3-phenylpropyl isovalerate, 3-phenylpropyl propionate, 4-((2-methyl-3- furyl)-thio)-5-nonanone, 4-(methylthio) butanal, 4-(methylthio) butanol, A- (methylthio)-2-butanone, 4-(methylthio)-4-methyl-2-pentanone, 4-(p- acetoxyphenyl)-2-butanone, 4,4-dibutyl-y-butyrolactone, 4,5-dimethyl-2-ethyl-3- thiazoline, 4,5-dimethyl-2-isobutyl-3-thiazoline,4-acetyl-6-t-butyl- 1, 1- dimethylindane, 4-heptanal diethyl acetal, 4-mercapto-2-butanone, 4-methyl-2- pentyl-1, 3-diαxolane, 4-methyl-5-thiazoleethanolacetate, 4-methylbiphenyl, A- phenyl-2-butyl acetate, 5- decenoic acid, 6-decenoic acid, 5-methoxy-3-ethyl- pyrazine, 6-methoxy-3-ethyl-pyrazine, 5-methoxy-3-methyl-pyrazine, 6-methoxy-3- methyl-pyrazine, 5,7-dihydro-2-methylthieno (3.4-d) pyrimidine, 5-ethyl-2-hydroxy- 3-methyl-cyclopent-2-en-l-one, 5-methyl-5-hexen-2-one, 5-phenyl-pentanol, 6- hydroxy-3, 7-dimethyloctanoic acid lactone, 6-methyl coumarin, 6-octenal, 7- ethoxy-4-methyl-coumarin, 7-methyl-4,4a,5,6-tetrahydro-2(3H)-naphthalenone, 9- undecenal, acetaldehyde benzyl methoxyethyl acetal, acetaldehyde butyl phenethyl acetal, acetaldehyde disopropyl acetal, acetaldehyde phenethyl propyl acetal, acetyl nonanoyl (2,3-undecadione), allyl 2-ethylbutyrate, allyl acetic acid (pentenoic acid), allyl anthranilate, allyl butyrate, allyl cinnamate, allyl crotonate, allyl cyclohexylacetate, allyl cyclohexylbutyrate, allyl cyclohexylhexanoate, allyl cyclohexylvalerate, allyl furoate, allyl heptanoate, allyl hexenoate, allyl isovalerate, allyl nonanoate, allyl octanoate, allyl phenoxyacetate, allyl phenylacetate, allyl propionate, allyl sorbate, allyl thiopropionate, allyl tiglate, allyll undecen-10-oate, allyl-x-ionone, anisyl phenylacetate, anisyl propionate, anisylactenone, benzaldehyde glyceryl acetate, benzaldehyde propyleneglycol acetal, benzoin, benzyl 2, 3-dimethyl-crotonate, benzyl butyl ether, benzyl isobutyl carbinol, benzyl isobutyl ketone, benzyl isoeugegenyl ether, benzyl phenylacetate, benzyl propyl carbinol, benzylidene methional, benzylidene methyl acetone, bis-(2,5-dimethyl-3- furyl) disulphide, bis-(2-methyl-3-furyl) disulphide, bis-(2-methyl-3-furyl) tetrasulphide, butan-3-one-2-yl butanoate, butyl 10-undecenoate, butyl 2-decenoate, butyl acetoacetate, butyl anthranilate, butyl butyrylglycollate, butyl butyryllactate, butyl cinnamate, butyl ethyl malonate, butyl levulinato, carvacryl ethylether, carvyl propionate, caryophylene alcohol acetate, cedryl acetate, cinnamaldehyde ethyleneglycol acetal, cinnamyl formate, cinnamyl isobutyrate, cinnamyl phenylacetate, cinnamyl propionate, cis-5-isopropenyl-cis-2-methylcyclo-pentan-l- carboxaldehyde, citral diethyl acetal, citral dimethyl acetal, citral propyleneglycol acetal, citronellyl oxyacetaldehyde, citronellyl phenylacetate, cyclocitral, cyclohexanecarboxylic acid, cyclohexyl acetic acid, cyclohexyl actetate, cyclohexyl anthranilate, cyclohexyl formate, cyclohexyl hexanoate, cyclohexyl isovalerate, cyclohexyl meroaptan, cyclohexyl methyl pyrazine, cyclohexyl propionate, cyclohexylbutyrate, cyclohexylcinnameta, cyclohexyl ethyl acetate, cyclopentanethiol, δ-damascone, δ-decalactone, decanal dimethyl acetal, dehydrodihydroinone, dehydrodihydroionol, di-(butan-3-one-l-yl) sulphide, diallyl poJysulphide, dibenzyl disulphide, dibenzyl ether, dibenzyl ketone (l,3-diphenyl-2- propanone), dibutyl sebacate, dicyclohexyl disulphide, diemthyl phenylethyl carbinyl acetate, diethyl sebacate, dimethyl phenyl carbinyl isobutyrate, dimethyl phenylethyl carbinyl isobutyrate, diphenyl disulphide, dodeca-3, 6-dienal, - dodecalactone, dodecyl isobutyrate, ethyl 10-undecenoate, ethyl 2,4- dioxohexanoate, ethyl 2-acetyl-3-phenylpropionate, ethyl 2-ethyl-3- phenylpropanoate, ethyl 2-methyl-3, 4-pentadienoate, ethyl 2-methyl-3-pentencate, ethyl 2-methyl-4-pentenoate, ethyl 2-methylpentanoate, ethyl 3-(furfrylthio) propionate, ethyl 3-oxohexanoate, ethyl 4-(methylthio)-butyrate, ethyl 4- phenylbutyrate, ethyl aconitate, ethyl benzoylacetate, ethyl butyryllaciate, ethyl cresoxyacetate, ethyl cyclohexanecarboxylate, ethyl cyclohexylproprionate, ethyl furylpropionate, ethyl isoeugenyl ether (isoeugenyl ethyl ether), ethyl maltol, ethyl methyl phenyl glycidate, ethyl n-ethylanthranilate, ethyl nitrite, ethyl octine carnonate (ethyl 2-nonynoate), ethyl phenylglycidate, ethyl-2-mercaptopropionate, ethyleneglycol tridecanedioic acid cyclic diester, ethylvanillin, eugenyl formate, furfuryl isopropyl sulphide, -furfuryl octanoate, furfuryl thipropionate, furfurylidene butanal, geranyl acetoacetate, geranyl phenylacetate, glucose pentaacetate, glyceryl 5-hydroxydecanoate, glyceryl 5-hydroxydodecanoate, guaiacyl phenylacetate, guaiyl acetate, heptanal dimethyl acetal, heptanal glyceryl acetal (2-hexyl-4- hydroxymethyl-1, 3-dioxolon and 2-hexyl-5-hydroxy-l, 3-dioxane), heptyl cinnamate, hexyl 2-furoate, hexyl 2-methyl-3(4)-pentenoate, hydroquinone monoethyl ether, hydroxycitronellal, hydroxycitronellal diethyl acetal, hydroxycitronellal dimethyl acetal, isoamyl acetoacetate, isoamyl cinnamate, isoamyl furylbutyrate, isoamyl furylpropionate, isoamyl pyruvate, isobornyl acetate, isobornyl anthranilate, isobornyl butyrate, isobornyl cinnamate, isobornyl formate, isobornyl isovalerate, isobornyl phenylacatate, isobornyl propionate, isobutyl acetoacetate, isobutyl furyl propionate, isobutyl phenylacetate, isobutyl salicylate, isoeugenyl acetate, isoeugenyl butyl ether, isoeugenyl formate, isoeugenyl phenylacetate, isojasmone, isopropyl cinnamate, isopropyl phenylacetate, isopropyl tiglate, isoquinoline, linalyl anthraniate, linalyl cinnamate, linalyl phenylacetate, rnaltyl isobutyrate, methoxypyrazine, methyl β-naphthyl ketone, methyl 1- acetoλycyclohexy ketone, methyl 4-(methylthio) butyrate, methyl 4-phenylbutyrate, methyl docine carbonate, methyl furfuracrylate, methyl heptine carbonate, methyl octine Cdibnonate, methyl p-tert-butylphenylactate, methyl styryl carbinol, methyl- isobutylcarbinyl acetate, -methyl-p-methoxy-cinnamaldehyde, n-ethyl-2-isopropyl- 5-methyl-cyclohexane carboxamide, nonanediol acetate, octanal dimethyl acetal, octyl formate, octyl phenylacetate, octylheptanoate, o-propylphenol, o-tolyl acetate, o-tolyl isobutyrate, o-tolyl salicylate, pentyl 2-furyl ketone, peperonyl acetate, p- sthoxybenzaldehyde, phenethyl 2-furoate, phenethyl anthranilate, phenetyl seneciate, phenoxyacetic acid, phenoxyethyl osibutyrate, phenyl ethyl methyl ethyl carbinol (l-phenyl-3-methyl-3-pentanol), phenylacetal dehyde 2, 3-butylene-glycol acetal, phenylacetaldehyde diisobutyl acetal, phenylacetaldehyde glycery acetal, phenylethyl methyl carninol (4-phenyl-2-butanol), piperonyl acetone, piperonyl isobutyrate, p-isopropyl phenyl acetaldehyde, p-methyl cinnamaldehyde, p- methylbenzyl acetone (4-(p-tolyl)-2-butanone), potassium 2- (T- ethoxy)ethoxypropanoate, p-propyl anisole, propenylguaethol, propyl 2-furoate, propyl 2-methyl-3 -furyl disulphide, propyl cinnamate, propyl furylacrylate, propyl thioacetate, propylene glycol dibenzoate, pseudo-cyclocitral, p-tolyl 3- methylbutyrate, p-tolyl isobutyrate, p-tolyl laurate, p-toiyl octanoate, p-tolyl phenylacetate, pyrazine ethanethiol, pyrazine methanethiol, pyrazinyl methyl sulphide, resorcinol dimethyl ether, rhodinyl acetate, rhodinyl isovalerate, rhodinyl phenylacetate, rhodinyl propionate, santalyl acetate, santalyl phenylacetate, s-methyl ionone, spiro (2,4-dithia-l-methyl-8-oxabicyclo (3,3,0) octane-3, 3'-(l'-oxa-2'- methyl)-cyclopentane), sucrose octaacetate, t-2-octenyl butanoate, teφinyl cinnamate, terpinyl isobutyrate, teφinyl isovalerate, tetrahydrofurfuryl acetate, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, tetrahydrolianlool, tetrahydro-pseudo-ionone, tetramethyl ethylcyclohexenone, thiogeraniol, tolualdehyde glyceryl acetal, trans-3-heptenyl acetate, trans-3-heptenyl isobutyrate, tributyl acetylcitrate, vanillin acetate, vanillin isobutyrate, vanillylidene acetone, vetiveryl acetate, x-amylcinnamaldehyde dimethyl acetal, x-amylcinnamic aldehyde, x-amylcinnamyl acetate, x- amylcinnamyl alcohol, x-amylcinnamyl formate, x-amylcinnamyl isovalerate, and x-butylcinnamaldehyde.

29. The composite according to either Claim 1 or 2, wherein the substrate is releases a compound chosen from: atorvastatin, montelukast, escitalopram, esomeprazole, levothyroxine, clopidogrel, metoprolol, lansoprazole, ezetimibe, simvastatin, fluticasone, cetirizine, venlafaxine, valsartan, alendronate, rosuvastatin, ievofloxadn, valsartan, duloxetine, pioglitazone, celecoxib, tamsulosin, quetiapine, amlodipiris, fenofibrate, sildenafil, ramipril, risedronate, Zolpidem, losartan, sarvedilol, valaciclovir, pregabalin, methylphenidate, risperidone, topiramate, varenicline, rosiglitazone, paclitaxel, olanzapine, sertraline, paroxetine, bupropion, citalopram, sumatriptan, fluconazole, mycophenolic acid, rabeprazole, terbinafϊne, lamotrigine, zoledronic acid, candesartan, famotidine, valdecoxib, fluoxetine, doxazosin, mirtazapine, efavirenz, felodipine, ranitidine, amphetamine, anastrozole. dorzolamide, lamivudine, ziprasidone, nevirapine, and zolmitriptan.

30. The composite according to either Claim 1 or 2, wherein the substrate is releases a compound chosen from: atorvastatin calcium, amlodipine besylate, pravastatin, venlafaxine, gabapentin, omeprazole, losartan, clopidogrel bisulphate, valsartan, azithromycin, sodium montelukast, fexofenadine hydrochloride, sodium enoxapariπ, ciprofloxacin hydrochloride monohydrate, docetaxel, clopidogrel bisulphate, quetiapine fumarate, sodium pravastatin, potassium amoxicillin-clavulanate, metoprolol, sodium pantoprazole, clarithromycin, ramipril, fluconazole, levofloxacin, gemcitabine, budesonide, zidovudine, raloxifene hydrochloride, nifedipine, candesartan cilexetil, tacrolimus, fluvastatin, tamsulosin hydrochloride, quinapril ydrochloride, peginterfron, piperacillin tazobactam, imipenem sodium cilastatin, levofloxacin, sodium diclofenac, ramipril, lisinopril, sodium fosinopril, ezetimibe, benazepril hydrochloride, and meropenem.

31. The composite according to either Claim 1 or 2, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix.

32. The composite according to either Claim 1 or 2, wherein the regenerated cellulose matrix has from about 80% to about 120% of the original molecular weight.

33. The composite according to either Claim 1 or 2, wherein the regenerated cellulose matrix has from about 90% to about 110% of the original molecular weight.

ZA. The composite according to either Claim 1 or 2, wherein the regenerated cellulose matrix has from about 90% to about 95% of tSe original molecular weight.

35. The composite according to either Claim 1 or 2, wherein the regenerated cellulose matrix has from about 95% to about 99% of the original molecular weight.

36. The composite according to either Claim 1 or 2, having less than about 10% by weight of residual ionic liquid.

37. The composite according to either Claim 1 or 2, having less than about 10% by weight of residual ionic liquid.

38. The composite according to either Claim 1 or 2, having less than about 10% by weight of residual ionic liquid.

39. The composite according to either Claim 1 or 2, having less than about 10% by weight of residual ionic liquid.

40. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix with a linker that is from 1 to 20 atoms in length.

41. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker comprises a substituted or unsubstituted, branched or unbranched, alkyl, alkenyl, or alkynyl group, ether, ester, polyether, polyester, polyalkylene, polyamines, heteroatom substituted alkyl, alkenyl, or alkynyl group, cycloalkyl group, cycloalkenyl group, heterocycloalkyl group, or heterocycloalkenyl group.

42. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker comprises a C₁-C₆ branched or straight-chain alkyl, a C₁-C₆ branched or straight-chain alkoxyl, or a C₂- C₆ branched or straight-chain alkyl where one or more of the carbon atoms is substituted with oxygen or an amino group.

43. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker prior to crosslinking the substrate comprises a dialdehyde, paraformaldehyde, epoxide, a dione, a diester, or a diisocyanate.

44. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker prior to crosslinking the substrate comprises 1,3-phenyldiisocyanate, 1,4-phenyldiisocyanate, 1,4- oyclohexyldiisocyanate, toluene diisocyanate, or 1 ,6-hexane-diisocyanate.

45. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker prior to crosslinking the substrate comprises an organo-halide.

46. The composite according to any of Claims 1-39. wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker prior to crosslinking the substrate comprises epichlorohydrin.

47. The composite according to any of Claims 1-39, wherein the substrate is crosslinked with a linker to the regenerated cellulose matrix and the linker prior to crosslinking the substrate comprises a hydrazine, an amine, an alcohol, a carboxylate, or a thiol.

48. The composite according to any of Claims 1 -39, wherein the substrate is crosslinked to one or more other substrates with a linker, with a linker is from 1 to 20 atoms in length.

49. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker comprises a substituted or unsubstituted, branched or unbranched, alkyl, alkenyl, or alkynyl group, ether, ester, polyether, polyester, polyalkylene, polyamines, heteroatom substituted alkyl, alkenyl, or alkynyl group, cycloalkyl group, cycloalkenyl group, heterocycloalkyl group, or heterocycloalkenyl group.

50. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker comprises a Ci-C₆ branched or straight-chain alkyl, a Ci-C₆ branched or straight-chain alkoxyl, or a C₂- C₆ branched or straight-chain alkyl where one or more of the carbon atoms is substituted with oxygen or an amino group.

51. The composite according to any of Claims 1 -39, wherein the substrate is crosslinked to one or more other substrates with a linker- and the linker prior to crosslinking the first active substrates comprises a dialdehyde, paraformaldehyde, epoxide, a dione, a diester, or a diisocyanate.

52. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker prior to crosslinking the first active substrates comprises 1,3-phenyldiisocyanate, 1,4-phenyldiisocyanate, i,4-cyclohexyldiisocyanate, toluene diisocyanate, or 1 ,6-hexane-diisocyanate.

53. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker prior to crosslinking the first active substrates comprises an organo-halide.

54. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker prior to crosslinking the substrates comprises epichlorohydrin.

55. The composite according to any of Claims 1-39, wherein the substrate is crosslinked to one or more other substrates with a linker, and the linker prior to crosslinking the substrates comprises a hydrazine, an amine, an alcohol, a carboxylate, or a thiol.

56. The composite according to any of Claims 1-39, wherein the substrate is capable of releasing a protein, nucleic acid, antibacterial, antiviral, cardiovascular therapeutic, anti-cancer therapeutic, CNS therapeutic, hypoglycemic agent, fertility/contraception or woman's health agent, infectious disease therapeutic, pulmonary disease therapeutic, or neutralizing agent.

57. The composite according to any of Claims 1-39, wherein the substrate is capable of releasing a microbial cell, herbicide, an insecticide, a fungicide, a microbial cell, a repellent for an animal or insect, a plant growth regulator, a fertilizer, a flavor or odor composition, a catalyst, a photoactive agent, an indicator, a dye, an UV adsorbent, or a mixture thereof.

58. The composite according to any of Claims 1-39, wherein the substrate is capable of releasing a biomolecule.

59. The composite according to Claim 58, wherein the biomolecule comprises a peptide, protein, enzyme, antibody, nucleic acid, aptamer, or ribozyme.

60. The composite according to any of Claims 1-39, wherein the substrate is capable of releasing a wetting agent.

61. The composite according to Claim 60, wherein the wetting agent comprises oleyl alcohol or cetyl alcohol.

62. A substrate having the formula:

wherein R is an anchoring unit chosen from: i) hydrogen; ii) Cj-C₁₂ linear, branched, or cyclic alkyl; iii) C₆ or Cio aryl; and iv) C₇-Cj₂ alkylenearyl; each L unit is independently chosen from: i) -(CR¹³R¹¹V; and ii) -(CR^2aR^2b)_x[X(CR^3aR^3b)_y]₂X-; the index w is from 1 to 50, the index x is from 0 to 50, the index y is from 2 to 12, the index z is from 1 to 20; R^la and R^lb are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl;

R^2a, R^2b, R^3a, and R^3b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; iii) -(CR⁵¹¹R⁵¹O_jOH; and iv) -[(CR^6aR^6b)_kNH₂;

R^5a, R , R^6a, and R^6b are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; the indices j and k are each independently from 2 to 20; each X is independently chosen from i) -C-; ii) -NK⁷-; iϋ) -S-; iv) -C(O)- ; v) -NHC(O)-; vi) -C(O)NH-; vii) -OC(O)-; and viii) -C(O)O-;

R⁷ is a ZA unit, a second bond to a ZA unit which serves to act together with the other bond to form a double bond, hydrogen, C₁-C₄ alkyl, or a unit having the formula -[(CR^8aR^8b)_mNH]_n(CR^9aR^9b)_pNH₂;

R^8a, R^8b, R^9a, and R^9b are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; the index m is from 2 to 20; the index n is from 0 to 6; the index p is from 2 to 20; each Z unit is independently a biohydrolyzable linking group; each A unit is independently a component of a physiologically active compound such that when the biohydrolyzable linking group is hydrolyzed, a physiologically active compound is released; and the index s is 1 or 2.

63. The substrate according to Claim 62, wherein R is phenyl or benzyl.

64. The substrate according to Claim 62, wherein R is ethyl.

65. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-(CH₂)_W- wherein the index w is from 2 to 20.

66. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-[CH₂CH(CH₃)]_W- or -[CH(CH₃)CH₂]_W- wherein the index w is from 2 to 20.

57. The substrata according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-(CH₂)_x[O(CH₂)_y]_zO- wherein the index x is from 1 to 6, the index y is from 2 to 6, and the index z is from 2 to 12.

68. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-(CH₂)_X[O(CH₂CH(CH₃))]_ZO- or -(CH₂)_X[O(CH(CH₃)CH₂)]_ZO- wherein the index x is from 1 to 6, and the index z is from 2 to 12.

69. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-(CH₂)_X[O(CH₂CH(CH₃))]_ZN- or -(CH₂)_X[O(CH(CH₃)CH₂)]_ZN- wherein the index x is from 1 to 6, and the index z is from 2 to 12.

70. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-(CH₂)_X[NR⁷(CH₂CH₂)]_Z-; wherein R⁷ has the formula: -[CH₂CH₂NH]_nCH₂CH₂NH₂; wherein the index n is from O to 6.

71. The substrate according to any of Claims 62-64, wherein L¹, L², and L³ each have the formula:

-[NHC(O)CH[(CH₂)₄NH₂)]_ZNH-; wherein the index z is from 1 to 10.

72. The substrate according to Claim 62, wherein each Z-A is independently chosen from: i) -(CR^10aR^10b)_qC(O)-A; ii) -C(O)(CR^10aR^10b)_qC(O)-A; iii) -<CR^!0aR^10b)_qC(O)O-A; iv> -OC(O)(CR^10aR^10b)_qCiO)O~A; v) -<CR^1OaR^1Ob)_qNH-A; vi) -NH(CR^i0aR^10b)_qC(O)-A; vii) -(CR^10aR^10b)_qC(O)NH-A; viii) -NHOC(O)(CR^10aR^10b)_qC(O)O-A;

IX)

x)

::i)

xii)

R^1Oa and R^IOb are each independently chosen from: i) hydrogen; and ii) C₁-C₂ alkyl; and the index q is from O to 10.

73. A substrate according to Claim 62, wherein the substrate has the formula:

R^1Oa and R^1Ob are each independently chosen from: i) hydrogen; and ii) Ci-C₂ alkyl; and the index q is from 0 to 10; and the index q is from 0 to 10; the index s is 1 or 2; the indices z¹ + z² + z³ = z..

74. The substrate according to Claim 62, wherein the index x = 1 ; and the indices z¹ + z² + z³ = z; z is from 5 to 6.

75. The composite according to Claim 62, wherein the index x = 1 ; and the indices z¹ +

6.

76. The substrate according to Claim 62, wherein the substrate has the formula:

the indices z¹ + z² + z³ = z.

77. The substrate according to Claim 76, wherein the index x = 1 ; and the indices z¹ + z² + z³ = z, z is from 5 to 6.

78. The substrate according to Claim 62, wherein the substrate releases a physiologically active compound having the formula:

wherein A is chosen from: i) C₁-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl;

• v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted C₁-C_2O heterocyclic; and vii) substituted or unsubstituted Ci-C₂₀ heteroaryl.

79. The substrate according to Claim 62, wherein the substrate releases a physiologically active compound having the formula:

wherein A is chosen from: i) Ci-C_2O substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C_2O aryl; v) substituted or unsubstituted C₇-C_2O alkylenearyl; vi) substituted or unsubstituted C₁-C₂₀ heterocyclic; and vii) substituted or unsubstituted Ci-C_2O heteroaryl.

80. The substrate according to Claim 62, wherein the substrate releases a physiologically active compound having the formula:

HO-A wherein A is chosen from: i) C₁-C₂₀ substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C₂₀ substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted Ci-C₂₀ heterocyclic; and vii) substituted or unsubstituted C i -C₂₀ heteroaryl.

81. The substrate according to any of Claims 62-80, wherein the substrate releases a fragrance raw material.

82. The substrate according to Claim 62, wherein the substrate has the formula:

wherein A is chosen from: i) C₁-C_2O substituted or unsubstituted, linear, branched or cyclic alkyl; ii) C₂-C_2O substituted or unsubstituted, linear, branched or cyclic alkenyl; iii) C₂-C_2O substituted or unsubstituted, linear or branched alkynyl; iv) substituted or unsubstituted C₆-C₂₀ aryl; v) substituted or unsubstituted C₇-C₂₀ alkylenearyl; vi) substituted or unsubstituted Ci-C₂₀ heterocyclic; and vii) substituted or unsubstituted C _\ -C₂o heteroarylC _\ -C₂₀ heteroaryl.

83. The substrate according to any of Claims 62-83, wherein the substrate releases a compound chosen from Phenoxymethylpenicillin potassium (Veetids); Oxacillin sodium (Bactocill); Benzylpenicillin potassium (Pfizerpen); Phenethicillin potassium (Syncillin); Flucloxacillin sodium (Floxapen); Propicillin potassium; Benzylpenicillin benzathine hydrate (Bicillin L-A); Meticillin sodium (Staphcillin); Hetacillin potassium (Hetacin-K); Phenoxymethylpenicillin benzathine; Clindamycin phosphate (Cleocin); Clindamycin palmitate hydrochloride (Cleocin pediatric); Clindamycin hydrochloride (Cleocin hydrochloride); Lincomycin hydrochloride (Lincocin); Vancomycin (Vancoled); Quinupristin; Dalfopristin; Quinupristin - dalfopristin mixt; (Synercid); Novobiocin sodium (Albamycin); Arbekacin sulfate (Habekacin);Teicoplanin (Tagocid); and Mupirocin calcium hydrate (Bactroban); Carindacillin sodium (Geocillin); Pivmecillinam hydrochloride (Melysin); Carfecillin sodium; Aztreonam (Azactam); Carumonam sodium (Amasulin); Tobramycin (Tobracin); Amikacin sulfate (Amikin); Kanamycin monosulfate (Kantrex); Paromomycin sulfate (Humatin); Isepamicin sulfate (Isepacin); Spectinomycin hydrochloride (Trobicin); Colistin sodium methanesulfonate (Coly-Mycin M); Polymixin B sulfate (Aerosporin); and Ceftibuten (Cedax); Anhydrous ampicillin (Omnipe); Amoxicillin hydrate (Amoxil); Piperacillin sodium (Pentcilli); Bacampicillin hydrochloride (Spectrobid); Ampicillin hydrate (Amcill); Ciclacillin (Cyclapen-W); Sultamicillin tosilate (Unasy); Lenampicillin hydrochloride (Valacilli); Ampicillin sodium (Omnipen); Carbenicillin sodium (Geope); Talampicillin hydrochloride (Aseocilli); Mezlocillin sodium (Mezli); Ticarcillin sodium (Ticar); Aspoxicillin (Doyle); Cefaclor (Alenfral); Cefadroxil (Sumacef); Cefixime (Suprax); Cefotetan; Cefalexin (Keflex); Cefradine (Anspor); Cefazolin sodium (Ancef); Cefalotin sodium (Kefli);Cefapirin sodium (Cefadyl); Cefmetazole sodium (Zefazone); Cefoxitin sodium (Mefoxi); Cefuroxime axetil (Cefti); Cefuroxime sodium (Zinacef); Cefdinir; (Cefzo);Cefoperazone sodium (Cefobid); Cefotaxime sodium (Clafora); Cefpodoxime proxetil (Vanti); Ceftazidime (Fortaz); Ceftizoxime sodium (Cefizox); Ceftriaxone sodium (Rocephi); Cefluprenam N); Cefaloridine (Kefloridi); Cefepime dihydrochloride (Maxipime); Cefacetrile sodium (Celtol); Cefpirome sulfate (Cefrom); Cefotiam hexetil hydrochloride (Pansporin-T); Ceftezole sodium (Celosli); Cefpimizole sodium AAjicef); Cefditoren pivoxil (Meiact); Cefetamet pivoxil hydrochloride (Cefyl); Cefcapene pivoxil hydrochloride hydrate (Flomox); Cefovecin sodium; Cefteram pivoxil (Tomiro); Cefuzonam sodium; Cefbuperazone sodium (Keiperazo); Cefotiam hydrochloride (Cerado); Cefodizime sodium (Kenicef); Cefpiramide sodium A(Suncefal); Cefminox sodium (Meiceli); Cefaloglycin; Cefinatilen hydrochloride hydrate; Cefsulodin sodium (Takesuli); Cefamandole sodium (Kefdole); Cefazolin sodium hydrate; Cefotetan sodium (Cefota); Cefoselis sulfate (Winsef); Cefozopran hydrochloride (Firstci); Propylene glycolate cefatrizine (Seapuro); Cefroxadine (Oraspor); Flomoxef sodium (Flumari); Latamoxef sodium (Moxam); Netilmicin sulfate (Netromyci); Gentamicin sulfate (Garamyci); Dibekacin sulfate (Panimyci); Micronomicin sulfate (Sagamici); ekanamycin sulfate (Kanendomyci); Astromicin sulfate (Fortimici); Sisomicin sulfate (Sisepti); Ribostamycin sulfate Vistamyci); Fosfomycin calcium Fosmici); Fosfomycin sodium (Fosmicin S); Imipenem hydrate; Amoxicillin - potassium clavulanate combination; (Clavamox); Imipenem hydrate - cilastatin sodium (Primaxi); Piperacillin sodium (Pentcilli); Tazobactam; Panipenem; Biapenem (Omegaci); Doripenem hydrate; Faropenem sodium (Farom); Ampicillin sodium (Omnipen); Cilastatin sodium; Meropenem trihydrate (Merrem); Sulbactam sodium; Piperacillin hydrate; Clavulanate potassium; Piperacillin-tazobactam combination (Tazoci); and Panipenem-betamipron (Carbeni).

S^. The substrate according to any of Claims 62-83, wherein tHe substrate releases a fragrance raw material chosen from: methyl, 2,4-dimethyl-3-cyclohexene-l -methyl, 2,4-dimethyl cyclohexane methyl, 5,6-dimethyl-l-methylethenyl-bicyclo[2.2.1]hept- 5-ene-2-methyl, 2,4,6-trimethyl-3-cyclohexene-l -methyl, 4-(l- methylethyl)cyclohexylmethy1, α-3,3-trimethyl-2-norboranylmethyl, 1, 1-dimethyl- l-(4-methylcyclohex-3-enyl)methyl, ethyl, 2-phenylethyl, 2-cyclohexylethyl, 2-(o- methylphenyl)ethyl, 2-(m-methylphenyl)ethyl, 2-(p-methylphenyl)ethyl, 6,6- dimethylbicyclo[3.1.l]hept-2-ene-2-ethyl, 2-(4-methylphenoxy)ethyl, 3,3-dimethyl- Δ²-β-norbornanylethyl, 2-methyl-2-cyclohexylethyl, 1 -(4-isopropylcyclohexyl)ethyl, 1 -phenyl- 1 -hydroxyethyl, 1 , 1 -dimethyl-2-phenylethyl, 1 , 1 -dimethyl-2-(4- methylphenyl)ethyl, propyl, 1-phenylpropyl, 3-phenylpropyl, 2-phenylpropyl, 2- (cyclododecyl)-propan-l-yl, 2,2-dimethyl-3-(3-methylphenyl)propan-l-yl, 2-methyl- 3-phenylpropyl, 3-phenyl-2-propen-l-yl, 2-methyl-3-phenyl-2-propen-l-yl, α-n- pentyl-3-phenyl-2-propen-l-yl, ethyl-3-hydroxy-3-phenyl propionate, 2-(4- methylphenyl)-2-propyl, butyl, 3-methylbutyl, 3-(4-methylcyclohex-3-ene)butyl, 2- methyl-4-(2,2,3-trimethyl-3-cyclopenten-l-yl)butyl, 2-ethyl-4-(2,2,3- trimethylcyclopent-3-enyl)-2-buten- 1 -yl, 3-methyl-2-buten- 1 -yl, 2-methyl-4-(2,2,3- trimethyl-3-cyclopenten-l-yl)-2-buten-l-yl, 3-hydroxy-2-butanone, ethyl 3- hydroxybutyrate, 4-phenyl-3-buten-2-yl, 2-methyl-4-phenylbutan-2-yl, 4-(4- hydroxyphenyl)butan-2-one, 4-(4-hydroxy-3-methoxyphenyl)butan-2-one, pentyl, cis-3-pentenyl, 3-methylpentyl, 3-methyl-3-penten-l-yl, 2-methyl-4-phenylpentyl, 3-methyl-5-phenylpentyl, 2-methyl-5-phenylpentyl, 2-methyl-5-(2,3- dimethyltricyclo-[2.2.1.0(2,6)]hept-3-yl)-2-penten-l-yl, 4-methyl-l-phenyl-2-pentyl, (1 -methyl-bicyclo [2.1.1 ]hepten-2-yl)-2-methylpent- 1 -en-3-yl, 3-methyl- 1 - phenylpent-3-yl, 1 ,2-dimethyl-3-(l-methylethenyl)cyclopent-l-yl, 2-isopropyl-4- methyl-2-hexenyl, cis-3-hexen-l-yl, trans-2-hexen-l-yl, 2-isopropenyl-5-methyl-4- hexen-1-yl, 2-ethyl-2-prenyl-3-hexenyl, 2-ethylhexyl, l-hydroxymethyl-4- isopropenyl- 1 -cyclohexenyl, 1 -methyl-4-isopropenylcyclohex-6-en-2-yl, 6-methyl- 3-isopropenylcyclohex- 1 -yl, 1 -methyl-4-isopropenylcyclohex-3-yl, 4-iso-propyl- 1 - methylcyclohex-3-yl, 4-tert-butylcyclohexyl, 2-tert-butylcyclohexyl, 2-tert-butyl-4- methylcyclohexyl, 4-isopropylcyclohexyl, 4-methyl- 1 -( 1 -methylethyl)-3 - cyclohexen- 1 -yl, 2-(5,6,6-trimethyl-2-norbomyl)cyclohexyl, isobomybyclohexyl, 3,3,5-triraethylcyclohexyl, l-methyl-4-isopropylcyclohex-3-yl, 1 ,2-dimethyl-3-(l- methylethyl)-cyclohexan-l-yl, heptyl, 2,4-dimethylhept-l-yl, 2,4-dimethyl-2,6- heptandicnyl, 6,6-dimethyl-2-oxymethylbicyclo[3.1. l.]hept-2-en-l-yl, 4-methyl-2,4- beptadien- i -yl, 3,4,5,6,6-pentamethyl-2-heptyl, 3,6-dimethyl-3-vinyl-5-hepten-2-yl, 6,6-dimethyl-3-hydroxy-2-methylenebicyclo[3.1.1 ]heptyl, 1 ,7,7-trimethylbicyclo- [2.2. l]hept-2-yl, 2,6-dimethylhept-2-yl, 2,6,6-trimethylbicyclo[l .3.3]hept-2-yl, octyl, 2-octenyl, 2-methyloctan-2-yl, 2-methyl-6-methylene-7-octen-2-yl, 7- methyioctan-1-yl, 3,7-dimethyl-6-octenyl, 3,7-dimethvl-7-octenyl, 3,7-dimethyl-6- octen-1-yl, 3,7-dimethyl-2,6-octadien-l-yl, 3,7-dimethyl-2,6-octadien-l->], 3,7- :ϊimethyl-l,6-octadien-3-yl, 3,7-dimethyloctan-l-yl, 3,7-dimethyloctan-3 yl, 2,4- octadien-1-yl, 3,7-dimethyl-6-octen-3-yl, 2,6-dimethyl-7-octen-2-yl, 2,6-dimethyl- 5,7-octadien-2-yl, 4,7-dimethyl-4-vinyl-6-octen-3-yl, 3-methyloctan-3-yl, 2,6- dimethyloctan-2-yl, 2,6-dimethyloctan-3-yl, 3,6-dimethyloctan-3-yl, 2,6-dimethyl-7- octen-2-yl, 2,6-dimethyl-3,5-octadien-2-yl, 3-methyl- l-octen-3-yl, 7-hydroxy-3,7- dimethyloctanalyl, 3-nonyl, 6,8-dimethylnonan-2-yl, 3-(hydroxymethyl)-2- nonanone, 2-nonen-l-yl, 2,4-nonadien-l-yl, 2,6-nonadien-l-yl, cis-6-nonen-l-yl, 377-dimethyl-l,6-nonadien-3-yl, decyl, 9-decenyl, 2-benzyl-M-dioxa-5-yl, 2-decen- 1-yl, 2,4-decadien-l-yl, 4-methyl-3-decen-5-yl, 3,7,9-trimethyl-l,6-decadien-3-yl, undecyl, 2-undecen-l-yl, 10-undecen-l-yl, 2-dodecen-l-yl, 2,4-dodecadien-l-yl, 2,7,1 l-trimethyl-2,6,10-dodecatrien-l-yl, 3,7,1 l-trimethyl-l,6,10,-dodecatrien-3-yl, 3,7,1 l,15-tetramethylhexadec-2-en-l-yl, 3,7,1 l,15-tetramethylhexadec-l-en-3-yl, benzyl, p-methoxybenzyl, para-cymen-7-yl, 4-methylbenzyl, 3,4- methylenedioxybenzyl, 2-(methyl)carboxy- 1 -hydroxyphenyl, 2-(benzyl)carboxy- 1 - hydroxyphenyl, 2-(cis-3-hexenyl)-carboxy- 1 -hydroxyphenyl, 2-(n-pentyl)carboxy- 1 - hydroxyphenyl, 2-(2-phenylethyl)carboxy-l -hydroxyphenyl, 2-(n-hexyl)carboxy-l- hydroxyphenyl, 2-methyl-5-isopropyl-l-hydroxyphenyl, 4-ethyl-2-methoxyphenyl, 4-allyl-2-methoxy- 1 -hydroxyphenyl, 2-methoxy-4-( 1 -propenyl)- 1 -hydroxyphenyl, 4-allyl-2,6-dimethoxy- 1 -hydroxyphenyl, 4-tert-butyl- 1 -hydroxyphenyl, 2-ethoxy-4- methyl- 1 -hydroxyphenyl, 2-methyl-4-vinyl- 1 -hydroxyphenyl, 2-isopropyl-5-methyl- 1 -hydroxyphenyl, 2-(isopentyl)-carboxy- 1 -hydroxyphenyl, 2-(ethyl)carboxy- 1 - hydroxyphenyl, 6-(methyl)carboxy-2,5-dimethyl-l ,3-dihydroxyphenyl, 5-methoxy- 3-methyl- 1 -hydroxyphenyl, 2-tert-butyl-4-methyl- 1 -hydroxyphenyl, 1 -ethoxy-2- hydroxy-4-propenylphenyl, 4-methyl-l -hydroxyphenyl, 4-hydroxy-3- methoxybenzaldehyde, 2-ethoxy-4-hydroxybenzaldehyde, decahydro-2-naphthyl, 2,5,5-trimethyl-octahydro-2-naphthyl, 1 ,3,3-trimethyl-2-norbomyl, 3a,4,5,6,7,7a- hexahydro-2,4-dimethyl-4,7-methano-lH-inden-5-yl, 3a,4,5,6,7,7a-hexahydro-3,4- dimethyi-4,7-methano- l//-indeiir5-yl, 2-methyl-2-vinyl-5-(l-hydroxy- 1 - methylethyl)tetrahydrofuranyl, and β-caryophyllenyl.

35. The composite according to any of Claims 62-83, wherein the substrate releases a compound chosen from: α, α-dimethylphenethyl acetate, α, α-dimethylphenethyl butyrate, α, α-dimethylphenethyl formate, 3-methyl-4-phenyl-3-butene-2-one, 4- emthyl-l-phenyl-2-pentanone, α-ethylbenzyl butyrate, isoeugenyl benzylether, α- isomethylionone, β-isomethylionone, α-methyl cinnamaldehyde, α-methyl ionone, β-methyl ionone, α-methyl lactate, α-methylbenzyl butyrate, α-methylbenzyl formate, α-methylbenzyl isobutyrate, α-methylbenzyl propionate, β-naplyl anthranilate, β-naptyl ethylether, β-naptyl isobutyl ether, α-terpinyl anthranilate, o- (ethoxymethyl) phenol, l-(p-methoxyphenyl)-l-penten-3-one, 1, 4-nonanediol diacetate, 1 , 9-nonanedithiol, l,2,3-tris(rethocy)-ethoxy-propane, 1,2-butanedithiol, l,2-di(l'-ethoxyl) propane, 1,2-propanedithiol, 1,3-butanedithiol, 1,8-octanedithiol, 10-undecen-l-yl acetate, 10-undecenal, 1-ethylhexyl tiglate, l-phenyl-2-propyl butyrate, l-phenyl-3 or 5-propylpyrazole, 2-(l-methylpropyl) thiazole, 2-(2-butyl)-4, 5-dimethyl-3-thiazoline, 2-(3-phenylpropyl) pyridine, 2-(3-phenylpropyl), tetrahydrofuran, 2-(p-tolyl)-propanal, 2, 6-nonadienal diethyl acetal, 2,3 or 10- mercaptopinane, 2,3-butanedithiol, 2,4-dimethyl-2-pentenoic acid, 2,4-dimethyl-5- acetylthiazole, 2,5-dimethyl-2, 5-dihydroxy-l, 4-dithiane, 2,5-dimethyl-3-furanthiol, 2,5-dimethyl-3-thioisovaleryfuran, 2,5-dimetyl -3-thofuroylfuran, 2,6,6-trimethyl-l- cyclohexen-1 acetaldehyde, 2,6-dimethyl-3-(2-methyl-3-furyl) thio-4-heptanone, 2,6dimethyl-4-heptanol, 2,6-dimethyl-6-hepten-l-ol, 2,6-dimethyloctanal, 2-2- dithiodithiophene, 2-amyl-5 or keto-1, 4-dioxane, 2-benzofuran carbozaldehyde, 2- butyl-2-butenal, 2-butyl-5 or 6-keto-l, 4-dioxane, 2-ethocythiazole, 2-ethyl-l, 3, 3- trimethyl-2-norbornanol, 2-ethyl-2-heptanal, 2-ethylbutyl acetate, 2-ethylthiophenol, 2-furan-methanethiol formate, 2-hexylidene cyclopentanone, 2-hydroxy-2- cyclohexen-1-one, 2-hydroxy-3, 5,5-trimethyl-2-cyclohexenone, 2-hydroxymethyl- 6, 6-dimethyl-bioyclo (3,1,1) hept-2-enyl formate, 2-mercaptopropionic acid, 2- methoxy-5 or 6-isopropylpyrazine, 2-methyl 2-oxo-3-methylpentanoate, 2-methyl-3, 5 or 6-metnylthio-pyrazine, 2-methyl-3,5 or 6-furfurylthio-pyrazine, 2-methyl-3- furanthiol, 2-methyl-3-tolyl-propanal, 2-methyl-4-pentenoic acid, 2-methyl-4- phenyl-2-butanol, 2-methyl-4-pheylbutanal, 2-methyl-5-methoxythiazole, 2- methylallyl butyrate, 2-methyloctanl, 2-methylundecanal, 2-pentyl-l-butan-3-one, 2- phenyl-l ^propanol, 2-phenyl-3-(2-furyl)-prop-2-enal, 2-phenyl-3-carbethoxy furan, 2-phenyl-4-psntenal, 2-piienylpropanal, dimethyl acetal, 2-phenylpropionaldehyde, 2-phenylpropyl butyrate, 2-phenylpropyl isobutyrate, 2-pyridine methanethiol, 2- seo-butylcyclohexanone, 2-thienylmercaptan, 2-trans-6-trans-octadienal, 3-((2- mercapto- 1 -methylpropyl)thio)-2-butanol, 3-((2-methyl-3 -furyl)-thio)-4-heptanone, 3-(2-methylpropyl) pyridine, 3-(5-metrhyl-2-furyl) butanal, 3-(hydroxymethyl)-2- heptanone, 3-(hydroxymethyl)-2-octanone, 3-(methylthio) butanal, 3-(p-isopropyl)- phenyl propanal, 3,5,5-trimethylhexanal, 3,5,5-trimethylhexanol, 3.7-dimethyl-2, 6- oxtadienyl 2-ethylbutyrate, 3-acetyl-2, 5-dimethylfuran, 3-acetyl-2,5- dimethylthiophene, 3-benzyl-4-heptanone, 3-ethyl-2-hydroxy-4-methyl-cyclopent-2- en-l-one, 3-heptyl-5-methyl-2(3H)-furanone, 3-mercapto-2-butanol, 3-mercapto-2- butanone, 3-mercapto-2-pentanone, 3-methyl-2-phenylbutanal, 3-methyl-5-propyl-2- cyclohexene-1-one, 3-octen-2-ol, 3-oxobutanal dimethyl acetal, 3-phenyl-4- pentenal, 3-phenylpropyl formate, 3-phenylpropyl hexanoate, 3-phenylpropyl isobutyrate, 3-phenylpropyl isovalerate, 3-phenylpropyl propionate, 4-((2-methyl-3- furyl)-thio)-5-nonanone, 4-(methylthio) butanal, 4-(methylthio) butanol, 4- (methylthio)-2-butanone, 4-(methylthio)-4-methyl-2-pentanone, 4-(p- acetoxyphenyl)-2-butanone, 4,4-dibutyl-y-butyrolactone, 4,5-dimethyl-2-ethyl-3- thiazoline, 4,5-dimethyl-2-isobutyl-3-thiazoline,4-acetyl-6-t-butyl-l , 1- dimethylindane, 4-heptanal diethyl acetal, 4-mercapto-2-butanone, 4-methyl-2- pentyl-1, 3-dioxolane, 4-methyl-5-thiazoleethanolacetate, 4-methylbiphenyl, 4- phenyl-2 -butyl acetate, 5- decenoic acid, 6-decenoic acid, 5-methoxy-3-ethyl- pyrazine, 6-methoxy-3-ethyl-pyrazine, 5-methoxy-3-methyl-pyrazine, 6-methoxy-3- methyl-pyrazine, 5,7-dihydro-2-methylthieno (3,4-d) pyrimidine, 5-ethyl-2-hydroxy- 3-methyl-cyclopent-2-en-l-one, 5-methyl-5-hexen-2-one, 5-phenyl-pentanol, 6- hydroxy-3, 7-dimethyloctanoic acid lactone, 6-methyl coumarin, 6-octenal, 7- ethoxy-4-methyl-coumarin, 7-methyl-4,4a,5,6-tetrahydro-2(3H)-naphthalenone, 9- undecenal, acetaldehyde benzyl methoxyethyl acetal, acetaldehyde butyl phenethyl acetal, acetaldehyde disopropyl acetal, acetaldehyde phenethyl propyl acetal, acetyl nonanoyl (2,3-undecadione), allyl 2-ethylbutyrate, allyl acetic acid (pentenoic acid), allyl anthranilate, allyl butyrate, allyl cinnamate, allyl crotonate, allyl cyclohexylacetate, allyl cyclohexylbutyrate, allyl cyclohexylhexanoate, allyl cyclohexylvalerate, allyl furoate, allyl heptanoate, allyl hexenoate, allyl isovalerate, allyl nonanoate, allyl octanoate, allyl phenoxyacetate, allyl phenylacetate, allyl propionate, tillyl sorbate, allyl thiopjopionate, allyl tiglate, allyll undecen-10-oate, iillyl-x-ionone, anisyl phenylacetate, anisyl propionate, anisylactenone, benzaldehyde glyceryl acetate, benzaldehyde propyleneglycol acetal, benzoin, benzyl 2, 3-dimethyl-crotonate, benzyl butyl ether, benzyl isobutyl carbinol, benzyl isobutyl ketone, benzyl isoeugegenyl ether, benzyl phenylacetate, benzyl propyl oarbinol, benzylidene methional, benzylidene methyl acetone, bis-(2,5-dimethyl-3- iuryl) disulphide, bis-(2-methyl-3-furyl) disulphide, bis-(2-methyl-3-furyl) tetrasulphide, butan-3-one-2-yl butanoate, butyl 10-undecenoate, butyl 2-decenoate, butyl acetoacetate, butyl anthranilate, butyl butyrylglycollate, butyl butyryllactate, butyl cinnamate, butyl ethyl malonate, butyl levulinato, carvacryl ethylether, carvyl propionate, caryophylene alcohol acetate, cedryl acetate, cinnamaldehyde ethyleneglycol acetal, cinnamyl formate, cinnamyl isobutyrate, cinnamyl phenylacetate, cinnamyl propionate, cis-5-isopropenyl-cis-2-methylcyclo-pentan-l- carboxaldehyde, citral diethyl acetal, citral dimethyl acetal, citral propyleneglycol ■ acetal, citronellyl oxyacetaldehyde, citronellyl phenylacetate, cyclocitral, •jyclohexanecarboxylic acid, cyclohexyl acetic acid, cyclohexyl actetate, cyclohexyl dnthranilate, cyclohexyl formate, cyclohexyl hexanoate, cyclohexyl isovalerate, jyclohexyl meroaptan, cyclohexyl methyl pyrazine, cyclohexyl propionate, cyclohexylbutyrate, cyclohexylcinnameta, cyclohexylethyl acetate, cyclopentanethiol, δ-damascone, δ-decalactone, decanal dimethyl acetal, dehydrodihydroinone, dehydrodihydroionol, di-(butan-3-one-l-yl) sulphide, diallyl polysulphide, dibenzyl disulphide, dibenzyl ether, dibenzyl ketone (l,3-diphenyl-2- propanone), dibutyl sebacate, dicyclohexyl disulphide, diemthyl phenylethyl carbinyl acetate, diethyl sebacate, dimethyl phenyl carbinyl isobutyrate, dimethyl phenylethyl carbinyl isobutyrate, diphenyl disulphide, dodeca-3, 6-dienal, - dodecalactone, dodecyl isobutyrate, ethyl 10-undecenoate, ethyl 2,4- dioxohexanoate, ethyl 2-acetyl-3-phenylpropionate, ethyl 2-ethyl-3- phenylpropanoate, ethyl 2-methyl-3, 4-pentadienoate, ethyl 2-methyl-3-pentencate, ethyl 2-methyl-4-pentenoate, ethyl 2-methylpentanoate, ethyl 3-(furfrylthio) propionate, ethyl 3-oxohexanoate, ethyl 4-(methylthio)-butyrate, ethyl 4- phenylbutyrate, ethyl aconitate, ethyl benzoylacetate, ethyl butyryllaciate, ethyl cresoxyacetate, ethyl cyclohexanecarboxylate, ethyl cyclohexylproprionate, ethyl furylpropionate, ethyl isoeugenyl ether (isoeugenyl ethyl ether), ethyl maltol, ethyl methyl phenyl glycidate, ethyl n-ethylanthranilate, ethyl nitrite, ethyl octine carnonate (ethyl 2-nonynoate), ethyl phenylglycidatej ethyl-2-mercaptopropionate, ethyleneglycol tridecanedioic acid cyclic diester, ethylvanillin, eugenyl formate, furfuryl isopropyl sulphide, -furfuryl octanoate, furfuryl thipropionate, furfurylidene butanal, geranyϊ acetoacetate, geranyl phenylacetate, glucose pentaacetate, glyceryl 5-hydroxydecanoate, glyceryl 5-hydroxydodecanoate, guaiacyl phenylacetate, guaiyl acetate, heptanal dimethyl acetal, heptanal glyceryl acetal (2-hexyl-4- hydroxymethyl-1, 3-dioxolon and 2-hexyl-5-hydroxy-l, 3-dioxane), heptyl cinnamate, hexyl 2-furoate, hexyl 2-metbyl-3(4)-pentenoate, hydroquinone monoethyl ether, hydroxycitronellal, hydroxycitronellal diethyl acetal, hydroxycitronellal dimethyl acetal, isoamyl acetoacetate, isoamyl cinnamate, isoamyl furylbutyrate, isoamyl furylpropionate, isoamyl pyruvate, isobornyl acetate, isobornyl anthranilate, isobornyl butyrate, isobornyl cinnamate, isobornyl formate, isobornyl isovalerate, isobornyl phenylacatate, isobornyl propionate, isobutyl acetoacetate, isobutyl furyl propionate, isobutyl phenylacetate, isobutyl salicylate, isoeugenyl acetate, isoeugenyl butyl ether, isoeugenyl formate, isoeugenyl phenylacetate, isojasmone, isopropyl cinnamate, isopropyl phenylacetate, isopropyl tiglate, isoquinoline, linalyl anthraniate, linalyl cinnamate, linalyl phenylacetate, maltyl isobutyrate, methoxypyrazine, methyl β-naphthyl ketone, methyl 1 - acetoxycyclohexy ketone, methyl 4-(methylthio) butyrate, methyl 4-phenylbutyrate, methyl docine carbonate, methyl furfuracrylate, methyl heptine carbonate, methyl octine carbnonate, methyl p-tert-butylphenylactate, methyl styryl carbinol, methyl- isobutylcarbinyl acetate, -methyl-p-methoxy-cinnamaldehyde, n-ethyl-2-isopropyl- 5-methyl-cyclohexane carboxamide, nonanediol acetate, octanal dimethyl acetal, octyl formate, octyl phenylacetate, octylheptanoate, o-propylphenol, o-tolyl acetate, o-tolyl isobutyrate, o-tolyl salicylate, pentyl 2-furyl ketone, peperonyl acetate, p- ethoxybenzaldehyde, phenethyl 2-furoate, phenethyl anthranilate, phenetyl seneciate, phenoxyacetic acid, phenoxyethyl osibutyrate, phenyl ethyl methyl ethyl carbinol (l-phenyl-3-methyl-3-pentanol), phenylacetal dehyde 2, 3-butylene-glycol acetal, phenylacetaldehyde diisobutyl acetal, phenylacetaldehyde glycery acetal, phenylethyl methyl carninol (4-phenyl-2-butanol), piperonyl acetone, piperonyl isobutyrate, p-isopropyl phenyl acetaldehyde, p-methyl cinnamaldehyde, p- methylbenzyl acetone (4-(p-tolyl)-2-butanone), potassium 2- (I¹- ethoxy)ethoxypropanoate, p-propyl anisole, propenylguaethol, propyl 2-furoate, propyl 2-methyl-3-furyl disulphide, propyl cinnamate, propyl furylacrylate, propyl thioacetate, propylene glycol dibeszoate, pseudo-cyclocitfal, p-tolyl 3- methylbutyrate, p-tolyl isobutyrate, p-tolyl laurate, p-tolyl octanoate, p-tolyl phenylacetate, pyrazine ethanethiol, pyrazine methanethiol, pyrazinyl methyl sulphide, resorcinol dimethyl ether, rhodinyl acetate, rhodinyl isovalerate, rhodinyl phenylacetate, rhodinyl propionate, santalyl acetate, santalyl phenylacetate, s-methyl ionone, spiro (2,4-dithia-l-methyl-8-oxabicyclo (3,3,0) octane-3. 3'-(r-oxa-2'- methyl)-cyclopentane), sucrose octaacetate, t-2-octenyl butanoate, teφinyl cinnamate, teφinyl isobutyrate, teφinyl isovalerate, tetrahydrofurfuryl acetate, tetrahydrofurfuryl butyrate, tetrahydrofurfuryl cinnamate, tetrahydrofurfuryl propionate, tetrahydrolianlool, tetrahydro-pseudo-ionone, tetramethyl ethylcyclohexenone, thiogeraniol, tolualdehyde glyceryl acetal, trans-3-heptenyl acetate, trans-3-heptenyl isobutyrate, tributyl acetylcitrate, vanillin acetate, vanillin isobutyrate, vanillylidene acetone, vetiveryl acetate, x-amylcinnamaldehyde dimethyl acetal, x-amylcinnamic aldehyde, x-amylcinnamyl acetate, x- amylcinnamyl alcohol, x-amylcinnamyl formate, x-amylcinnamyl isovalerate, and x-butylcinnamaldehyde.

The composite according to any of Claims 62-83, wherein the substrate releases a compound chosen from simvastatin, salmeterol, fluticasone, rofecoxib, peginterferon, conjugated estrogenic hormones, ondansetron hydrochloride, fluticasone, conepezil, paclitaxel, risedronate, bicalutamide, irbesartan, ipratropium bromide, meloxicam, Lamivudine, Zidovudine, abacavir, levothyroxine, finasteride, fenofibrate, budesonide, formoterol fumarate, tolterodine, mometasone fliroate, ipratropium, orlistat, propofol, losartan, salbutamol, and stavudine.

87. The composite according to any of Claims 62-83, wherein the substrate is releases a compound chosen from: olanzapine, esomeprazole, sertraline, paroxetine, alendronate, omeprazole, celecoxib, sildenafil, bupropion, rosiglitazone, Zolpidem , citalopram, pioglitazone hydrochloride, sumatriptan succinate, fluconazole, lansoprazole, tamsulosin, mycophenolate mofetil, rabeprazole, terbinafine, paclitaxel, tamsulosin hydrochloride, lamotrigine, zoledronic acid, candesartan cilexetil, valaciclovir, famotidine, desloratidine, valdecoxib, fluoxetine, doxazosin mesylate, mirtazapine, carvedilol, efavirenz, tenofovir diisoproxil fumarate, felodipine, ranitidine, ranitidine, amphetamine, anastrozole, dorzolamide, lamivudine, pioglitazone, ziprasidone hydrochloride, nevirapine, and" zolrnitriptan.

88. The composite according to any of Claims 62-83, wherein the substrate is releases a compound chosen from: atorvastatin, montelukast, escitalopram, esomeprazole, levothyroxine, clopidogrel, metoprolol, lansoprazole, ezetimibe, simvastatin, fluticasone, cetirizine, venlafaxine, valsartan, alendronate, rosuvastatin, levofloxacin, valsartan, duloxetine, pioglitazone, celecoxib, tamsulosin, quetiapine, amlodipine, fenofibrate, sildenafil, ramipril, risedronate, Zolpidem, losartan, carvedilol, valaciclovir, pregabalin, methylphenidate, risperidone, topiramate, varenicline, rosiglitazone, paclitaxel, olanzapine, sertraline, paroxetine, bupropion, citalopram, sumatriptan, fluconazole, mycophenolic acid, rabeprazole, terbinafine, lamotrigine, zoledronic acid, candesartan, famotidine, valdecoxib, fluoxetine, doxazosin, mirtazapine, efavirenz, felodipine, ranitidine, amphetamine, anastrozole, dorzolamide, lamivudine, ziprasidone, nevirapine, and zolmitriptan.