Glucose-sensitive cationic hydrogels for insulin release

Poly(diethylaminoethyl methacrylate-g-ethylene glycol) hydrogels were prepared having a molar ratio of 10:1 diethylaminoethyl methacrylate to poly(ethylene glycol) of molecular weights 200, 400 and 1000 Da. The hydrogels were prepared using tetra(ethylene glycol) dimethacrylate to give a crosslinking ratio between 0.5–4.0 %. Glucose oxidase and catalase was immobilized in the matrix during polymerization. The maximum enzyme loading used was 6.6 × 10 −4 g of glucose oxidase/g of polymer. The hydrogels were prepared in the form of discs and microparticles. The properties of these hydrogels were investigated in terms of their equilibrium and dynamic swelling properties. The pH-dependent equilibrium swelling characteristics showed a sharp transition between the swollen and the collapsed state at a pH of 7.0. The dynamic response of the hydrogel discs to pH was found to be slow. The microparticle on the other hand showed rapid swelling and collapse under the influence of pulsatile pH changes. The effects of particle size and crosslinking and molecular weight of PEG on the dynamic swelling response were investigated. The glucose-sensitive behavior of the gels due to glucose oxidase was also studied. It was found that the response of the hydrogels to glucose was dependent on the crosslinking ratio and the enzyme loading. The pulsatile nature of the response under varying glucose conditions was also investigated. Diffusion and relaxation models were used to predict swelling of single microparticles under different pH and glucose conditions. These swelling models were used in conjunction with a diffusion model for insulin to predict release profiles. It was found that the initial rate of release was very high followed by an asymptotic increase to a steady rate of release. These materials were found to have desirable properties for glucose-sensitive insulin delivery in the body. They were suitable for further clinical testing on animals for the development of next degeneration delivery devices