Glucose and H2O2 Dual-Responsive Polymeric Micelles for the Self-Regulated Release of Insulin

In the past decades, insulin delivery systems have been widely developed for diabetes treatment. Though a few works have investigated polymeric micelles with glucose and H2O2 dual-responsiveness for the delivery of insulin, great efforts should still be devoted to enhancing the therapeutic efficacy. Herein, glucose/H2O2 dual-responsive polymeric micelles were fabricated for the self-regulated insulin delivery. The polymeric micelles were self-assembled by poly(ethylene glycol)-block-poly(amino phenylboronic ester) (PEG-b-PAPBE), where the hydrophilic PEG offered the shell and the hydrophobic PAPBE endowed the polymeric micelles with the dual-sensibility to glucose and H2O2. The built-in phenylboronic ester (PBE) could be not only broken by glucose but also hydrolyzed by H2O2, thus resulting in the disintegration of the polymeric micelles. The glucose-responsive release of insulin was achieved and could be further facilitated by the coencapsulation of glucose oxidase (GOx) in the micelles, which would produce H2O2 by catalytic oxidation of glucose and thus lead to the hydrolysis of the phenylboronic ester by H2O2. Compared with free insulin or micelles that carried insulin alone, a subcutaneous injection of the insulin/GOx-coloaded polymeric micelles to the diabetic mice presented a superior hypoglycemic effect in vivo. This kind of polymeric micelle with glucose and H2O2 dual-responsiveness provides a promising approach for diabetes therapy.