Hypoxia and H₂O₂ Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery

A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients’ health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H 2 O 2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles ( d -GRPs) can disassociate and subsequently release insulin triggered by H 2 O 2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d -GRPs were able to eliminate the excess H 2 O 2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.