An artificial “closed-loop” system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein, 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 (Figure 1). 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 (Figure 1). <i>In vitro</i> studies validated that the release of insulin from nanovesicle was effectively correlated with the external glucose concentration. <i>In vivo</i> 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 (&lt;200 mg/dL) for up to 5 days.

Bio-inspired synthetic vesicles for glucose-responsive insulin delivery

249th National Meeting (2015)

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