Modulated insulin delivery from glucose-sensitive hydrogel dosage forms.

Glucose-sensitive hydrogels that undergo sol-gel phase transition were used to develop modulated insulin delivery systems. Glucose-sensitive hydrogels were prepared by mixing glucose-containing polymers and PEGylated concanavalin A (Con A). Glucose was incorporated into the polymer backbone by copolymerization of allyl glucose with comonomers, such as 3-sulfopropylacrylate, potassium salt (SPAK), N-vinyl pyrrolidone (VP), and acrylamide (AM). Con A grafted with five PEG molecules were used to improve the stability of Con A. Three different types of insulin delivery systems were examined: diffusion-controlled reservoir, diffusion-controlled matrix, and erosion-controlled matrix systems. Insulin release through the glucose-sensitive hydrogel membrane and from the glucose-sensitive hydrogel matrix was dependent on the glucose concentration in the receptor chamber. As the glucose concentration was increased from 1 to 4 mg/ml, the release rate increased. The insulin release rate decreased as the glucose concentration was reduced to 1 mg/ml. Modulated insulin release was achieved using the glucose-sensitive membrane and matrix systems. On the other hand, the glucose-sensitive erodible system did not show modulated release as the glucose concentration was changed between 1 and 4 mg/ml.