A glucose-responsive complex polymeric micelle enabling repeated on–off release and insulin protection

We developed a glucose-responsive complex polymeric micelle (CPM) through the self-assembly of two types of diblock copolymers, poly(ethylene glycol)-b-poly(aspartic acid-co-aspartamidophenylboronic acid) (PEG-b-P(Asp-co-AspPBA)) and poly(N-isopropylacrylamide)-b-poly(aspartic acid-co-aspartamidophenylboronic acid) (PNIPAM-b-P(Asp-co-AspPBA)). By controlling the weight ratio between PNIPAM and PEG (WPNIPAM/WPEG = 6/4), the block copolymers form complex micelles with a novel core–shell–corona structure. By following this structure, the continuous PNIPAM shell collapsed on the glucose-responsive P(Asp-co-AspPBA) core. As a result, the CPM exhibits a reversible swelling in response to changes in the glucose concentration, enabling the repeated on–off release of insulin regulated by glucose level. Furthermore, the CPM could effectively protect the encapsulated insulin against protease degradation. Therefore, this glucose-responsive CPM provides a simple and powerful strategy to construct a self-regulated insulin delivery system for diabetes treatment.