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

Abstract

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.