An injectable and glucose-sensitive nanogel for controlled insulin release

Abstract

Glucose-responsive polymer gels provide an attractive option for the design of a self-regulated insulin delivery system. Here, this paper reported the biocompatibility, glucose-sensitive behavior, and in vivo application of a dispersion of nanogels with three interpenetrating polymer networks of poly(N-isopropylacrylamide), dextran and poly(3-acrylamidophenylboronic acid) (P(NIPAM–Dex–PBA)). The nanogels had an average hydrodynamic radius of about 150 nm, and particle size increased with increasing content of dextran. The swelling behavior of the nanogels at different glucose concentrations revealed definite glucose sensitivity of P(NIPAM–Dex–PBA) particles. Furthermore, the analysis of relative cell proliferation suggested that the nanogels had good biocompatibility with L-929 mouse fibroblast cells. The loading amount of insulin, as a model drug, was up to 16.2%, and the drug release was dependent on the composition of dextran in the particles and the concentration of glucose present in release medium. In vivo experiments revealed that insulin-loaded nanogels decreased the blood glucose levels in diabetic rats and maintained 51% of the baseline level for almost 2 hours. The hypoglycemic effect of the drug-loaded nanogels was similar to that of free insulin after administration. Importantly, the drug-loaded nanogels could keep blood glucose levels stable and avoided blood sugar fluctuations compared with free insulin.