Nanostructured Gels Capable of Controlled Release of Encapsulated Agents

Abstract

Self-assembled gel compositions including a gelator, e.g., an enzyme-cleavable gelator, e.g., having a molecular weight of 2500 or less, are described. The self-assembled gel compositions can encapsulate one or more agents. Methods of making the self-assembled gel compositions, and methods of drug delivery using the self-assembled gel compositions are also described.

1 . A self-assembled gel composition comprising an enzyme-cleavable, generally recognized as safe (GRAS) first gelator having a molecular weight of 2500 or less, wherein the GRAS first gelator is selected from the group consisting of ascorbyl alkanoate, sorbitan alkanoate, triglycerol monoalkanoate, sucrose alkanoate, glycocholic acid, and any combination thereof, and wherein the GRAS first gelator self-assembles into a gel comprising nano structures. 
     
     
         2 . (canceled) 
     
     
         3 . The self-assembled gel composition of  claim 1 , wherein the ascorbyl alkanoate comprises ascorbyl palmitate, ascorbyl decanoate ascorbyl laurate, ascorbyl caprylate, ascorbyl myristate, ascorbyl oleate, or any combination thereof. 
     
     
         4 .- 6 . (canceled) 
     
     
         7 . The self-assembled gel composition of  claim 1 , wherein the triglycerol monoalkanoate comprises triglycerol monopalmitate, triglycerol monodecanoate, triglycerol monolaurate, triglycerol monocaprylate, triglycerol monomyristate, triglycerol monostearate, triglycerol monooleate, or any combination thereof. 
     
     
         8 . (canceled) 
     
     
         9 . The self-assembled gel composition of  claim 1 , wherein the sucrose alkanoate comprises sucrose palmitate, sucrose decanoate, sucrose laurate, sucrose caprylate, sucrose myristate, sucrose oleate, or any combination thereof. 
     
     
         10 .- 11 . (canceled) 
     
     
         12 . The self-assembled gel composition of  claim 1 , further comprising a non-independent gelator, wherein the non-independent second gelator co-assembles with the GRAS first gelator to form the self-assembled gel. 
     
     
         13 .- 17 . (canceled) 
     
     
         18 . The self-assembled gel composition of  claim 1 , wherein the nanostructures are lamellar. 
     
     
         19 . The self-assembled gel composition of  claim 1 , further comprising one or more agents that are encapsulated within the nanostructures, non-covalently bonded to the nanostructures, or both. 
     
     
         20 . (canceled) 
     
     
         21 . The self-assembled gel composition of  claim 19 , wherein the one or more agents are selected from the group consisting of: a steroid, an anti-inflammatory agent, a chemotherapeutic, a poly ADP-ribose polymerase inhibitor, a polypeptide, a nucleic acid, a polynucleotide, a polyribonucleotide, an anti-pain agent, an anti-pyretic agent, an anti-depression agent, a vasodilator, a vasoconstrictor, an immune-suppressant, a tissue regeneration promoter, a vitamin, a small interfering RNA, a polymer selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), hyaluronic acid, chitosan, carboxy methylcellulose, poly(ethylene glycol) di-acrylate, and poly(glycerol-co-sebasate acrylate), and any combination thereof. 
     
     
         22 .- 26 . (canceled) 
     
     
         27 . A method of forming a self-assembled gel composition of  claim 1 , the method comprising:
 combining the GRAS first gelator and a solvent to form a mixture;   heating or sonicating the mixture;   stirring or shaking the mixture for a time sufficient to form a homogeneous solution; and   cooling the homogenous solution for a time sufficient to enable the formation of a self-assembled gel composition.   
     
     
         28 . A method of forming a self-assembled gel composition of  claim 1 , the method comprising:
 combining the enzyme-cleavable GRAS first gelator and a solvent to form a mixture;   and   (i) one or both of heating or sonicating the mixture, for and cooling the mixture for a time sufficient to enable the formation of a self-assembled gel composition; or (ii) adding an aqueous solution to the mixture to form the self-assembled gel composition, wherein the solvent in the mixture is an organic solvent.   
     
     
         29 .- 36 . (canceled) 
     
     
         37 . A self-assembled gel composition comprising an enzyme-cleavable, generally recognized as safe (GRAS) first gelator having a molecular weight of 2500 or less and a non-independent second gelator. 
     
     
         38 . The self-assembled gel composition of  claim 1 , wherein the GRAS first gelator is selected from the group consisting of ascorbyl alkanoate, triglycerol monoalkanoate, glycocholic acid, and any combination thereof. 
     
     
         39 . The self-assembled gel composition of  claim 1 , wherein the gel composition comprises vitamin(s) or vitamin derivative(s). 
     
     
         40 . The self-assembled gel composition of  claim 19 , wherein the GRAS first gelator is a liquid GRAS gelator and is present in the gel composition at a concentration of 0.01-15 wt %, and the one or more agents are present in a concentration of 0.1-10 wt %. 
     
     
         41 . The self-assembled gel composition of  claim 19 , wherein the one or more agents are selected from the group consisting of a nutraceutical, a flavoring agent, a sensor, an enzyme, an agent that potentiates an efficacy of one or more remaining agents, insulin, a dye, a cosmetic agent, a drug, an anticancer agent, an agent that can promote cell migration, an agent that can promote cell proliferation, an agent that can promote matrix production, an agent that can promote cell differentiation, an agent that can promote cell reprogramming, an anti-apoptosis agent, an agent that can alter metabolism, an anti-coagulant, a blood thinner, an antioxidant agent, a sleep medication, an enzyme inhibitor, and any combination thereof. 
     
     
         42 . The self-assembled gel composition of  claim 1 , wherein the GRAS first gelator can form both hydrogels and organogels. 
     
     
         43 . The self-assembled gel composition of  claim 1 , wherein the composition is a hydrogel in a microparticle, nanoparticle, coating, or film form. 
     
     
         44 . A method for controllably releasing one or more agents in a subject, the method comprising administering to a subject a composition of  claim 19 . 
     
     
         45 . The method of  claim 44 , wherein the one or more agents are released topically for cosmetic or therapeutic purposes. 
     
     
         46 . The self-assembled gel composition of  claim 37 , wherein the non-independent gelator is a vitamin derivative. 
     
     
         47 . The self-assembled gel composition of  claim 46 , wherein the vitamin-derivative comprises vitamin A ester, retinyl acetate, retinyl palmitate, alpha tocopherol acetate, or vitamin D. 
     
     
         48 . The self-assembled gel composition of  claim 37 , wherein the gel comprises lamellar nanostructures. 
     
     
         49 . The self-assembled gel composition of  claim 37 , wherein the gel comprises nanostructures and further comprises one or more agents that are encapsulated within the nanostructures, non-covalently bonded to the nanostructures, or both. 
     
     
         50 . The self-assembled gel composition of  claim 49 , wherein the GRAS first gelator is a liquid GRAS gelator and is present in the gel at a concentration of 0.01-15 wt %, and the one or more agents are present in a concentration of 0.1-10 wt %. 
     
     
         51 . The self-assembled gel composition of  claim 49 , wherein the one or more agents are selected from the group consisting of a steroid, an anti-inflammatory agent, a chemotherapeutic, a poly ADP-ribose polymerase inhibitor, a polypeptide, a nucleic acid, a polynucleotide, a polyribonucleotide, an anti-pain agent, an anti-pyretic agent, an anti-depression agent, a vasodilator, a vasoconstrictor, an immune-suppressant, a tissue regeneration promoter, a vitamin, a small interfering RNA, a polymer selected from the group consisting of poly(ethylene glycol), poly(ethylene oxide), hyaluronic acid, chitosan, carboxy methylcellulose, poly(ethylene glycol) di-acrylate, and poly(glycerol-co-sebasate acrylate), and any combination thereof. 
     
     
         52 . The self-assembled gel composition of  claim 49 , wherein the one or more agents is selected from the group consisting of a nutraceutical, a flavoring agent, a sensor, an enzyme, an agent that potentiates an efficacy of one or more remaining agents, insulin, a dye, a cosmetic agent, a drug, an anticancer therapy, an agent that can promote cell migration, an agent that can promote cell proliferation, an agent that can promote matrix production, an agent that can promote cell differentiation, an agent that can promote cell reprogramming, an anti-apoptosis agent, an agent that can alter metabolism, an anti-coagulant, a blood thinner, an antioxidant agent, a sleep medication, an enzyme inhibitor, and any combination thereof. 
     
     
         53 . The self-assembled gel composition of  claim 37 , wherein the composition is a hydrogel in a microparticle, nanoparticle, coating, or film form. 
     
     
         54 . A method for controllably releasing one or more agents in a subject, the method comprising administering to a subject a composition of  claim 49 . 
     
     
         55 . The method of  claim 54 , wherein the one or more agents are released topically for cosmetic or therapeutic purposes.