Glucose and pH Dual-Responsive Polymersomes with Multilevel Self-Regulation of Blood Glucose for Insulin Delivery

Smart insulin delivery systems now play essential roles in diabetes treatment, whereas most existing systems suffer from insufficient regulation against blood glucose. Here, a glucose and pH dual-responsive insulin delivery system with multilevel self-regulation of blood glucose was constructed. Photocross-linked dual-responsive polymersomes were prepared by the self-assembly of the diblock copolymer methoxyl poly(ethylene glycol)-b-poly[3-acrylamidophenylboronic acid-co-2-(diethylamino)ethyl methacrylate-co-2-hydroxy-4-(methacryloyloxy)benzophenone] (mPEG-b-P(AAPBA-co-DEAEMA-co-BMA)) synthesized by reversible addition-fragmentation chain transfer polymerization (RAFT), where insulin and glucose oxidase (GOx) were co-encapsulated inside. It is worth noting that the polymersomes with tunable membrane permeability are the first glucose-responsive platform consisting of both PBA and GOx. According to the pH change produced by gluconic acid, the pH-sensitive monomer DEAEMA endowed the polymersome membrane with multilevelly tunable and self-regulative permeability, further controlling the release behavior of insulin. This multilevel tunability was reflected directly in in vitro insulin release tests and was proven by the self-regulation of blood glucose in vivo. Promisingly, the polymersomes have great potential to be applied for the self-regulation of blood glucose in the treatment of diabetes.