(327e) Development of Thermally-Responsive Composite Poly(2-hydroxyethyl methacrylate)-Hydroxypropyl Cellulose Hydrogels

Thermally sensitive poly(2-hydroxyethyl methacrylate)-hydroxypropyl cellulose, or PHEMA-HPC, composite hydrogels were investigated for use in medical treatment of cancer. We explored HPC as a thermally sensitive component of a hydrogel device for heating-activated drug release, using a model drug, theophylline, to guide the structural development. The composite hydrogel is created by blending a mixture of HEMA monomer and HPC with crosslinking agent ethylene glycol dimethacrylate (EGDMA) and reacted by free radical solution polymerization. In the resulting PHEMA-HPC composite hydrogel, the HPC fills the void space to slow diffusion when the HPC is expanded at temperatures below its lower critical solution temperature (LCST). HPC with molecular weights of 10, 100, and 370 kDa were found to have LCSTs of 41, 45 and 48 oC, respectively. When the composite hydrogel is heated in aqueous solution, HPC phase separates and contracts as it surpasses its LCST. This causes a change in the structure of the hydrogel, showing a decrease in mass. In this study, composite gels were made with 5:1, 20:1 and 80:1 mass ratio of HEMA to HPC at each of the HPC molecular weights, and the gels were synthesized both below (37 oC) and above (57 oC) the LCST of HPC investigate the effect of reaction conditions on the structure of the composite gels. Diffusion coefficients determined from the release experiments and showed an increase to increase with reaction temperature. The mechanical structure of the composite gels was investigated by both equilibrium swelling and mechanical testing, with the effective mesh sizes of the composite gels determined by either Flory-Rehner theory or rubber elasticity data. By developing materials which show a reliable positive thermal response to release a drug when heated, magnetic nanoparticles can be imbedded into the hydrogels to activate release by application of a radio frequency magnetic field. These composite materials could thus be used in a combination therapy device that combines magnetic hyperthermia and localized triggered chemotherapy for treatment of tumor cells.