Bio-Inspired Synthetic Nanovesicles for Glucose-Responsive
Release of Insulin
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Abstract
A new glucose-responsive formulation
for self-regulated insulin
delivery was constructed by packing insulin, glucose-specific enzymes
into pH-sensitive polymersome-based nanovesicles assembled by a diblock
copolymer. Glucose can passively transport across the bilayer membrane
of the nanovesicle and be oxidized into gluconic acid by glucose oxidase,
thereby causing a decrease in local pH. The acidic microenvironment
causes the hydrolysis of the pH sensitive nanovesicle that in turn
triggers the release of insulin in a glucose responsive fashion. In
vitro studies validated that the release of insulin from nanovesicle
was effectively correlated with the external glucose concentration.
In vivo experiments, in which diabetic mice were subcutaneously administered
with the nanovesicles, demonstrate that a single injection of the
developed nanovesicle facilitated stabilization of the blood glucose
levels in the normoglycemic state (<200 mg/dL) for up to 5 days