Glucose-Responsive Micelles for Controlled Insulin Release Based on Transformation from Amphiphilic to Double Hydrophilic.

Abstract

Recently, stimuli-responsive carriers have been paid much attention to control cargo release due to their obvious advantages such as targeted delivery, reduced systematic cytotoxicity and enhanced therapeutic efficiency. In this study, a well-defined block copolymer synthesized via ATRP, i.e., poly(ethylene glycol)-b-poly(2-diisopropylaminoethyl methacrylate) (PEG-b-PDPA), has been used to investigate the insulin release behavior in response to glucose changes for potential diabetes mellitus (DM) therapy. Based on the enzymatic catalytic reaction of glucose and glucose oxidase (GOD), the acidic product (gluconic acid) can reduce the micro-environmental pH value. Thereby, the hydrophobic PDPA block with pH sensitivity can rapidly be protonated in response to the decrease of pH value. Due to the partial protonated PDPA block undergoing a variation from hydrophobic to hydrophilic, the self-assembled nanomicelle can gradually release loaded insulin in a regulated model. According to the characterizations of size, morphology, drug loading efficiency, controlled insulin release behavior, glucose sensitivity and cytotoxicity, we conclude that this delicately designed glucose-responsive nanomicelle would be an efficient self-regulated carrier for controlled insulin release for potential DM therapy.