Sustained Drug Release by Thermoresponsive Sol-Gel Hybrid Hydrogels of Poly(N-Isopropylacrylamide-co-3-(Trimethoxysilyl)Propyl Methacrylate) Copolymers.

Poly(N-isopropylacrylamide-co-3-(trimethoxysilyl)propyl methacrylate), P(NIPAAm-co-TMSPMA), copolymers with relatively high TMSPMA contents without insoluble fraction are successfully synthesized. Subsequent sol-gel reactions in both the absence and presence of tetraethyl orthosilicate lead to gels with high gel fractions. The resulting gels undergo gel collapse at 28.6-28.7 °C, i.e., below that of poly(N-isopropylacrylamide) homopolymer of 34.3 °C. Unexpectedly, the theophylline-loaded hybrid gels release the drug not only below but also above the gel collapse temperature (GCT) with considerable rates and released amounts of drug. Surprisingly, evaluation of the sustained release profiles by the Korsmeyer-Peppas equation indicates that the release occurs by Fickian diffusion above GCT, which can be attributed to the lack of significant drug-polymer interaction at such temperatures. These results can be widely applied for the design and utilization of TMSPMA-based sol-gel polymer hybrids with desired release profiles of solutes below and above GCT for a variety of applications.