Thermosensitive Hydrogels: Design and Characterization of Phase-Separating Materials

Thermosensitive hydrogels of N-isopropylacrylamide (NIPAAm) copolymerized with other monomers such as acrylamide will be synthesized by free-radical polymerization and characterized to determine their suitability for use in triggered-release chemotherapy systems. Reaction parameters such as co-monomer type and composition and cross-linking ratio will be varied. The hydrogels will be tested to tune their lower critical solution temperature, LCST, so that the gels phase separate above the normal human body temperature of 37°C. Poly(N-isopropylacrylamide) (PNIPAAm) is negatively thermosensitive, that is, it swells at low temperatures and collapses with increasing temperature. At its LCST, PNIPAAm collapses precipitously, but the LCST for PNIPAAm is 32-34°C. Co-polymerizing NIPAAm with other hydrophilic monomers increases its LCST, but adding too much co-monomer also decreases the sharpness of the transition temperature range, so the amount of co-monomer added must be optimized. Higher cross-linking ratios result in a tighter mesh structure, allowing greater control of drug release, even for small molecular weight agents. The overall goal of the project is to develop oligomers based on NIPAAm that can be grafted onto networks of another non-thermosensitive hydrogel, poly(2-hydroxyethylmethacrylate) (PHEMA) so the oligomers can be used as gateways to control the release of various chemotherapeutic agents imbedded in the PHEMA matrix.