Phenylboronic acid grafted chitosan as a glucose-sensitive vehicle for controlled insulin release.

To develop self-regulated insulin delivery system, the glucose-sensitive copolymers with a fraction of phenylboronic acid group were prepared by the coupling reaction of -COOH of N-(carboxyacyl) chitosan and -NH(2) of 3-aminophenylboronic acid. A sufficient glucose sensitivity of the copolymer was accomplished by the glucose-induced volume changes of the nanoparticles and release profiles of insulin in phosphate buffered saline (PBS, pH 7.4) with different glucose concentrations, which occurred in a remarkable glucose concentration-dependent manner. Furthermore, circular dichroism spectroscopy demonstrates that the overall tertiary structure of the released insulin was not altered compared with that of the standard insulin. The analysis of relative cell proliferation suggests that the copolymer showed good cytocompatibility. The glucose-sensitive copolymers have a potential use in self-regulated drug-releasing systems.