(112b) Glucose-Responsive Systems for Insulin Delivery Based on Poly(Ethylene Glycol)-Containing, pH-Sensitive, Cationic Hydrogels

Cationic hydrogels were investigated for intelligent, glucose responsive drug delivery in the blood system. Crosslinked hydrogels of poly(diethylaminoethyl methacrylate-g-ethylene glycol) were synthesized using comonomer ratios, ranging from 10:1 to 80:1 repeating units of diethylaminoethyl methacrylate (DEAEM) to grafted chains of poly(ethylene glycol). These gels contained specified amounts of glucose oxidase and catalase. The gels were crosslinked with 2 wt % tetraethylene glycol dimethacrylate. Experiments were carried out to characterize the structure and pH-sensitivity of these hydrogels. Mesh sizes were obtained experimentally as a function of pH, and found to increase with decreasing pH. The molecular weight between crosslinks was also calculated at varying comonomer ratios and found to increase with increasing DEAEM content. The equilibrium swelling behavior of these ionic hydrogels was examined in buffer solutions at pH values ranging from 3.2 to 8.0. These experiments showed that as the pH was decreased, there was a general trend toward increased swelling ratio with increased presence of the pH-sensitive component, DEAEM. Oscillatory swelling studies were performed and the response of the gels to changes in external pH was investigated. Also studies of responsive behavior were performed in various glucose solutions. Diffusion studies were performed using solutes with varying sizes and membrane diffusion coefficients determined.