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.