Environmentally Responsive Hydrogels for Delivery

Abstract

A nanosensor-containing polymer composition for the monitoring of physiological parameters and a method for making the composition are disclosed. The composition includes a fluid nanosensor-containing polymer that becomes rigid in the presence of physiological conditions. In the fluid form, the composition can be suitable for injection on to or into the skin. In the rigid form, the nanosensor is substantially immobilized in the polymer. The method includes forming a mixture comprising a nanosensor and polymer precursor(s), subjecting the mixture to conditions suitable for forming the fluid form of the composition; and subjecting the fluid form to physiological conditions to provide a rigid nanosensor-containing composition.

1 . A method, comprising:
 forming a mixture comprising a nanosensor, a first monomer, a second monomer and an initiator, wherein the nanosensor comprises a nanoparticle having a detectable label, wherein the nanoparticle interacts with a specific analyte present in a transdermal environment;   subjecting the mixture to conditions suitable for copolymerization of the first monomer and second monomer to provide a nanosensor-containing copolymer in a fluid form;   subjecting the nanosensor-containing copolymer in fluid form to a temperature above the copolymer's lower critical solution temperature to provide a nanosensor-containing copolymer in a rigid form.   
     
     
         2 . The method of  claim 1 , wherein the first monomer has the structure of formula (III): 
       
         
           
           
               
               
           
         
         wherein
 R is a hydrophilic group; and 
 R 1  is hydrogen or methyl. 
 
       
     
     
         3 . The method of  claim 2 , wherein the first monomer has the structure of formula (IIIa): 
       
         
           
           
               
               
           
         
         wherein
 X is —O—, —NR′— or —S—; 
 y is 0-10; 
 R 1  is hydrogen or methyl; and 
 R 2  is hydrogen, —C 1 -C 12 alkyl, —C 1 -C 12 alkyl-OH, —SiR′ 3 , —C(O)—C 1 -C 12 alkyl, —C 1 -C 12 alkyl-C(O)OR′, wherein R′ is —C 1 -C 12 alkyl. 
 
       
     
     
         4 . The method of  claim 3 , wherein R 1  is methyl. 
     
     
         5 . The method of  claim 3 , wherein the first monomer comprises poly(ethylene glycol) methyl ether methacrylate. 
     
     
         6 . The method of  claim 2 , wherein the second monomer has the structure of formula (IV): 
       
         
           
           
               
               
           
         
         wherein
 R 3  is a hydrophobic group; and 
 R 4  is hydrogen or methyl. 
 
       
     
     
         7 . The method of  claim 6 , wherein R 3  is —C 1 -C 12 alkyl, -cycloalkyl, or aryl. 
     
     
         8 . The method of  claim 6 , wherein R 4  is methyl. 
     
     
         9 . The method of  claim 6 , wherein the second monomer comprises N-isopropylacrylamide. 
     
     
         10 . The method of  claim 1 , wherein the detectable label comprises a fluorophore. 
     
     
         11 . The method of  claim 1 , wherein the mixture comprises a 90:10 ratio of first monomer to second monomer. 
     
     
         12 . The method of  claim 1 , wherein the mixture comprises an 80:20 ratio of first monomer to second monomer. 
     
     
         13 . The method of  claim 1 , wherein the mixture comprises a 70:30 ratio of first monomer to second monomer. 
     
     
         14 . The method of  claim 1 , wherein the mixture comprises a 60:40 ratio of first monomer to second monomer. 
     
     
         15 . The method of  claim 1 , wherein the mixture comprises a 50:50 ratio of first monomer to second monomer. 
     
     
         16 . The method of  claim 1 , wherein subjecting the nanosensor-containing copolymer in the fluid form to a temperature above the copolymer's lower critical solution temperature comprises introducing the nanosensor-containing copolymer in the fluid form into the intradermal environment. 
     
     
         17 . The method of  claim 14 , wherein introducing the nanosensor-containing copolymer in the fluid form into the intradermal environment comprises transdermally delivering the nanosensor-containing copolymer in the fluid form into the intradermal environment through one or more microneedles. 
     
     
         18 . A composition, comprising:
 a nanosensor comprising a nanoparticle having a detectable label, wherein the nanosensor interacts with a specific analyte in an intradermal environment; and   a polymer, wherein the polymer changes from a fluid form to a rigid form in response to crosslinking;   wherein the nanosensor is disposed in the polymer.   
     
     
         19 . The composition of  claim 18 , wherein the crosslinking can be initiated by a component in the intradermal environment. 
     
     
         20 . The composition of  claim 18 , wherein the polymer comprises alginic acid.