Design, synthesis, and degradation studies of new enzymatically erodible poly(hydroxyethyl methacrylate)/poly(ethylene oxide) hydrogels

This work describes the synthesis and the study of poly(hydroxyethyl methacrylate) PHEMA hydrogels, cross-linked by poly(ethylene oxide)(PEO) chains containing the Gly-Gly-Leu tripeptide. This sequence was selected for its ability to be cleaved by subtilisin, a bacterial protease. The cross-linker was synthesized by coupling the peptide with two amino-terminated PEO chains of M(w)=3400 g/mol. The resulting polymer was characterized by size exclusion chromatography, nuclear magnetic resonance, and mass spectroscopy, and was shown to be readily cleaved by subtilisin. Its esterification of the hydroxyl end groups into methacrylate afforded a macromonomer that was used as a degradable cross-linker and copolymerized with hydroxyethylmethacrylate to form hydrogels. The swelling ratio of the gels increases when the PEO cross-linker/polyHEMA ratio increases. Incubation of these gels with the enzyme led to the total degradation of the gels. These assays show that these gels can be used as drug-delivery systems where the release is triggered by the presence of proteases.