Glucose-Triggered Insulin Release from Fe3+-Cross-linked Alginate Hydrogel: Experimental Study and Theoretical Modeling

We study the mechanisms involved in the release, triggered by the application of glucose, of insulin entrapped in Fe3+-cross-linked alginate hydrogel particles further stabilized with a polyelectrolyte. Platelet-shaped alginate particles are synthesized containing enzyme glucose oxidase conjugated with silica nanoparticles, which are also entrapped in the hydrogel. Glucose diffuses in from solution, and production of hydrogen peroxide is catalyzed by the enzyme within the hydrogel. We argue that, specifically for the Fe3+-cross-linked systems, the produced hydrogen peroxide is further converted to free radicals via a Fenton-type reaction catalyzed by the iron cations. The activity of free radicals, as well as the reduction of Fe3+ by the enzyme, and other mechanisms contribute to the decrease in density of the hydrogel. As a result, while the particles remain intact, void sizes increase and release of insulin ensues and is followed experimentally. A theoretical description of the involved processes is proposed and utilized to fit the data. It is then used to study the long-time properties of the release process that offers a model for designing new drug-release systems.