Drug Delivery Composition Comprising a Self-Assembled Gelator

Abstract

This invention discloses drug-delivery compositions, methods of making prodrugs, and methods of drug delivery using a self-assembled gelator. The backbone of the gelator can contain a drug or prodrug, such as acetaminophen or salicin. Additional drugs or agents can be encapsulated in the gelator. Enzymatic or hydrolytic cleavage can be used to release the drugs.

1 . A drug-delivery composition comprising a drug-derived or prodrug-derived gelator capable of self assembly in both aqueous and organic solvents, wherein the backbone of the gelator contains a drug or prodrug, or a derivative thereof, and which drug or prodrug can be released upon a stimulus. 
     
     
         2 . The composition of  claim 1 , wherein the stimulus is enzyme-mediated degradation or hydrolytic cleavage. 
     
     
         3 - 8 . (canceled) 
     
     
         9 . The composition of  claim 1 , wherein the backbone of the drug-derived gelator contains the drug or a derivative thereof, a hydrophobic or hydrophilic moiety, and a degradable link between the drug and the hydrophobic or hydrophilic moiety. 
     
     
         10 - 16 . (canceled) 
     
     
         17 . The composition of  claim 1 , wherein the gelator is the esterification reaction product of the drug and a C 1-22  carboxylic acid. 
     
     
         18 . (canceled) 
     
     
         19 . The composition of  claim 1 , wherein the drug contains a phenol ring and/or a terminal hydroxyl group, and wherein the drug is capable of undergoing self assembly upon esterification with a fatty acid or dicarboxylic acid. 
     
     
         20 - 24 . (canceled) 
     
     
         25 . The composition of claim  7 , wherein the drug-derived or prodrug-derived gelator is a single-component gelator that does not require any other complementary molecules or base salts to induce self-assembly. 
     
     
         26 . (canceled) 
     
     
         27 . The composition of  claim 1 , wherein the drug or prodrug is acetaminophen, salicin, indomethacin, or ethambutol. 
     
     
         28 - 35 . (canceled) 
     
     
         36 . The drug delivery composition of  claim 1 , further comprising an agent, wherein the agent is encapsulated in the gel of the gelator, and wherein the agent can be released upon exposure to an enzyme or upon hydrolytic cleavage of the gelator. 
     
     
         37 - 40 . (canceled) 
     
     
         41 . A gel composition, comprising an agent and a self-assembled gelator having an ester, amide, anhydride, or carbamate functionality and a hydrophobic moiety in the backbone of the gelator, wherein the agent is encapsulated in the gel of the gelator and can be released upon a stimulus. 
     
     
         42 . (canceled) 
     
     
         43 . The composition of  claim 41 , wherein the gelator is a tris-based hydrogelator having an amide functionality. 
     
     
         44 . (canceled) 
     
     
         45 . The composition of  claim 41 , wherein the gelator is of formula (IV): 
       
         
           
           
               
               
           
         
         wherein R is a saturated or unsaturated C 1-22  alkyl group, and R 1 , R 2 , and R 3  each independently represent a hydroxyalkyl group. 
       
     
     
         46 - 47 . (canceled) 
     
     
         48 . The composition of  claim 41 , wherein the gelator is a single-component gelator that does not require any other complementary molecules or base salts to induce self-assembly. 
     
     
         49 - 79 . (canceled) 
     
     
         80 . A single-step method of making a low molecular weight, amphiphilic prodrug, comprising the step of:
 (a) esterifying a compound having a phenol ring and terminal hydroxyl group with a dicarboxylic acid to form an amphiphilic prodrug containing an ester functionality; or   (b) esterifying a compound having a saccharide group, phenol ring and primary hydroxyl group with a vinyl ester of carboxylic acid to form an amphiphilic prodrug containing an ester functionality,   wherein the method does not comprise subsequent chemical reactions.   
     
     
         81 . The method of  claim 80 , wherein the esterification reaction takes place without the use of a catalyst. 
     
     
         82 - 88 . (canceled) 
     
     
         89 . The method of  claim 80 , wherein the compound is acetaminophen, indomethacin, or ethambutol. 
     
     
         90 - 96 . (canceled) 
     
     
         97 . A single-step method of making a low molecular weight, amphiphilic gelator, comprising the step of reacting a tris-hydroxyl methyl amine with a fatty acid or methyl ester to form an amphiphilic gelator having an amide functionality, wherein the method does not comprise subsequent chemical reaction steps. 
     
     
         98 - 108 . (canceled) 
     
     
         109 . The method of  claim 80 , wherein the esterification reaction takes place in presence of a Lipase enzyme. 
     
     
         110 - 112 . (canceled) 
     
     
         113 . The method of  claim 80 , wherein said amphiphilic prodrug is of formula (III): 
       
         
           
           
               
               
           
         
         wherein R is a saturated or unsaturated C 1-21  alkyl group. 
       
     
     
         114 . A method of drug delivery, comprising: administering to a patient in need thereof the drug delivery composition of  claim 1 , and contacting the drug delivery composition with an enzyme or water to cleave the degradable link and release the drug or prodrug in the patient. 
     
     
         115 - 118 . (canceled) 
     
     
         119 . The method of  claim 114 , wherein the drug or prodrug is delivered in a sustained release without burst release. 
     
     
         120 - 134 . (canceled) 
     
     
         135 . A method of drug delivery, comprising: administering to a patient in need thereof the gel composition of  claim 41  and contacting the composition with a suitable enzyme or water to cleave the amide bond in the gelator and release the drug or prodrug in the patient. 
     
     
         136 - 147 . (canceled) 
     
     
         148 . The method of claim  136 , wherein the enzyme is encapsulated in the gelator. 
     
     
         149 - 166 . (canceled) 
     
     
         167 . The drug-delivery composition of  claim 1 , wherein the drug-derived or prodrug-derived gelator comprises:
 (a) a compound of formula (I):   
       
         
           
           
               
               
           
         
         wherein n represents an integer from 1-22; 
         (b) a compound of formula (II): 
       
       
         
           
           
               
               
           
         
         wherein n represents an integer from 1-22; 
         (c) a compound of formula (III): 
       
       
         
           
           
               
               
           
         
         wherein R is a saturated or unsaturated C 1-21  alkyl group; 
         (d) a compound of formula (V): 
       
       
         
           
           
               
               
           
         
         wherein R is a peptide comprising 1-40 amino acids or R is saturated or unsaturated C 1-21  alkyl group; or 
         (e) a compound of formula (VI): 
       
       
         
           
           
               
               
           
         
         wherein R is a peptide comprising 1-40 amino acids or R is saturated or unsaturated C 1-21  alkyl group. 
       
     
     
         168 . A compound selected from the following:
 (a) a compound of formula (I):   
       
         
           
           
               
               
           
         
         wherein n represents an integer from 1-22; 
         (b) a compound of formula (II): 
       
       
         
           
           
               
               
           
         
         wherein n represents an integer from 1-22; 
         (c) a compound of formula (III): 
       
       
         
           
           
               
               
           
         
         wherein R is a saturated or unsaturated C 1-21  alkyl group; 
         (d) a compound of formula (V): 
       
       
         
           
           
               
               
           
         
         wherein R is a peptide comprising 1-40 amino acids or R is saturated or unsaturated C 1-21  alkyl group; or 
         (e) a compound of formula (VI): 
       
       
         
           
           
               
               
           
         
         wherein R is a peptide comprising 1-40 amino acids or R is saturated or unsaturated C 1-21  alkyl group. 
       
     
     
         169 . The composition of  claim 36 , wherein the agent can be released from gel in the absence of any stimulus, or without cleavage of the gelator. 
     
     
         170 . The method of  claim 114 , wherein the drug delivery composition comprises an encapsulated agent, and further comprising contacting the drug delivery composition with an enzyme or water to cleave the degradable link and release the drug or prodrug and the encapsulated agent simultaneously.