Materials for modulating biological responses and methods of making

Abstract

A polymeric composition capable of releasing nitric oxide and modulating biological responses comprises a biocompatible polymer and S-nitrosated thiol bonded to the biocompatible polymer. The polymeric composition can have a thiol conversion of at least 40%. The polymeric composition can also have a nitric oxide recovery of at least 40% when under thermal decomposition conditions.

The following is claimed: 
     
         1 . A polymeric composition capable of releasing nitric oxide and modulating biological responses, the composition comprising:
 a. a biocompatible polymer; and   b. S-nitrosated thiol bonded to the biocompatible polymer, wherein the polymeric composition has a thiol conversion of at least 40%.   
     
     
         2 . The polymeric composition of  claim 1 , wherein the biocompatible polymer is a synthetic polymer selected from the group consisting of: polylactide, polyglycolide, poly(lactide-co-glycolide) and poly(ε-caprolactone). 
     
     
         3 . The polymeric composition of  claim 1 , wherein the biocompatible polymer is a polysaccharide selected from the group consisting of: chitosan and dextran. 
     
     
         4 . The polymeric composition of  claim 1 , wherein the S-nitrosated thiol includes a thiol selected from the group consisting of cysteamine, cysteine, homocysteine, and combinations thereof. 
     
     
         5 . The polymeric composition of  claim 1 , wherein the S-nitrosated thiol includes a thiol selected from the group consisting of glutathione and penicillamine. 
     
     
         6 . The polymeric composition of  claim 1 , wherein the polymeric composition has a nitric oxide loading of at least 0.1 mmol/g polymer. 
     
     
         7 . The polymeric composition of  claim 1 , wherein the polymeric composition consists essentially of the biocompatible polymer, S-nitrosated thiol and optionally thiol residue, and wherein the polymeric composition has a nitric oxide recovery of at least 40% under thermal decomposition conditions. 
     
     
         8 . The polymeric composition of  claim 1 , wherein the polymeric composition consists essentially of the biocompatible polymer, S-nitrosated thiol and optionally thiol residue, and wherein the polymeric composition has a nitric oxide recovery of at least 60% when under thermal decomposition conditions. 
     
     
         9 . The polymeric composition of  claim 1 , wherein the polymeric composition has a nitric oxide recovery of at least 20% under physiological conditions for 48 hours. 
     
     
         10 . The polymeric composition of  claim 1 , wherein the biocompatible polymer is poly(lactide-co-glycolide), the S-nitrosated thiol includes a thiol selected from the group consisting of cysteamine, homocysteine and combinations thereof, and the thiol conversion is at least 90%. 
     
     
         11 . A polymeric composition capable of releasing nitric oxide and modulating biological responses, the composition comprising:
 a. a biocompatible polymer;   b. thiol residue bonded to the biocompatible polymer, and   c. S-nitrosated thiol bonded to the biocompatible polymer, wherein at least 40% of total thiol residue and S-nitrosated thiol present is S-nitrosated thiol.   
     
     
         12 . The polymeric composition of  claim 11 , wherein the biocompatible polymer is a synthetic polymer selected from the group consisting of: polylactide, polyglycolide, poly(lactide-co-glycolide) and poly(ε-caprolactone). 
     
     
         13 . The polymeric composition of  claim 11 , wherein the S-nitrosated thiol includes a thiol selected from the group consisting of cysteamine, cysteine, homocysteine, and combinations thereof. 
     
     
         14 . The polymeric composition of  claim 11 , wherein the biocompatible polymer is poly(lactide-co-glycolide) and the S-nitrosated thiol includes cysteamine. 
     
     
         15 . The polymeric composition of  claim 11 , wherein the biocompatible polymer is poly(lactide-co-glycolide) and the S-nitrosated thiol includes cysteine. 
     
     
         16 . The polymeric composition of  claim 11 , wherein the biocompatible polymer is poly(lactide-co-glycolide) and the S-nitrosated thiol includes homocysteine. 
     
     
         17 . The polymeric composition of  claim 11 , wherein the polymeric composition is capable of nitric oxide release over a period of at least 172 hours. 
     
     
         18 . The polymeric composition of  claim 11 , wherein the polymeric composition has a nitric oxide recovery of at least 40% under thermal dry conditions. 
     
     
         19 . The polymeric composition of  claim 11 , wherein the polymeric composition has a nitric oxide recovery of at least 20% under physiological conditions for 48 hours. 
     
     
         20 . The polymeric composition of  claim 11 , wherein at least 90% of total thiol residue and S-nitrosated thiol present is S-nitrosated thiol.