New terpolymers as hydrogels for oral protein delivery application

The purpose of this study is to develop novel intestinal-specific insulin delivery systems with pH-sensitive swelling and drug release properties. The glucose-6-acrylate- 1,2,3,4-tetraacetate (GATA) monomer was prepared under mild conditions. Cubane-1,4-dicarboxylic acid linked to two 2-hydroxyethyl methacrylate groups was the crosslinking agent (CA). Methacrylic-type polymeric prodrugs were synthesized by free-radical copolymerization of methacrylic acid (MAA), poly(ethylene glycol) monomethyl ether methacrylate, and GATA in the presence of cubane as a crosslinking agent. The composition of the crosslinked three-dimensional polymers was determined by FTIR spectroscopy. Equilibrium swelling studies were carried out in enzyme-free simulated gastric and intestinal fluids (SGF and SIF, respectively). Insulin was entrapped in these gels and the in vitro release profiles were established separately in both SGF (pH 1) and SIF (pH 7.4). Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. In these cases, the biological activity of insulin was retained. These results were used to design and improve protein release behavior from these carriers.