Glucose and H 2 O 2 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 H 2 O 2 dual-responsiveness for the delivery of insulin, great efforts should still be devoted to enhancing the therapeutic efficacy. Herein, glucose/H 2 O 2 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 H 2 O 2 . The built-in phenylboronic ester (PBE) could be not only broken by glucose but also hydrolyzed by H 2 O 2 , 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 H 2 O 2 by catalytic oxidation of glucose and thus lead to the hydrolysis of the phenylboronic ester by H 2 O 2 . 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 H 2 O 2 dual-responsiveness provides a promising approach for diabetes therapy.