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Glucose and H2O2 Dual-Responsive Polymeric Micelles for the Self-Regulated Release of Insulin
journal contribution
posted on 2020-02-24, 20:44 authored by Xiaoyu Liu, Chang Li, Juan Lv, Fan Huang, Yingli An, Linqi Shi, Rujiang MaIn 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.