In vitro and in vivo behavior of insulin delivery systems based on poly(ethylene glycol)-grafted poly(methacrylic acid) hydrogels
Developing oral insulin formulations for the treatment of diabetes can greatly improve the quality of life of the patients. Many different approaches have been investigated to address the problems associated with oral insulin delivery, but the bioavailability of oral insulin is still low, even in some of the most successful formulations. Insulin is rapidly degraded by the enzymes in the GI tract and is not transported across the epithelial barrier easily. The oral insulin formulation developed in this work makes use of complexation hydrogels for oral delivery of insulin bioconjugates. The insulin bioconjugates synthesized in this work consist of insulin bound to transferrin molecule which can be uptaken by the epithelial cells. These conjugates can increase the permeability of insulin across the epithelial barrier by receptor-mediated transcytosis. The transferrin in the conjugate is also shown to stabilize insulin in the presence of intestinal enzymes. Use of complexation hydrogels for delivery of insulin-transferrin conjugate may greatly increase the bioavailability of oral insulin. This is because, the complexation hydrogels are known to exhibit characteristics that make them ideal candidates for oral protein delivery. For example, it is shown in this work that the hydrogels can increase the retention of the therapeutic protein in the small intestine. They can also inhibit the degradation of insulin in the GI tract. Thus, combination of these two approaches provides an innovative platform for oral insulin delivery.