Bioresponsive Microneedles with a Sheath Structure for H₂ O₂ and pH Cascade-Triggered Insulin Delivery

Self-regulating glucose-responsive insulin delivery systems have great potential to improve clinical outcomes and quality of life among patients with diabetes. Herein, an H₂ O₂ -labile and positively charged amphiphilic diblock copolymer is synthesized, which is subsequently used to form nano-sized complex micelles (NCs) with insulin and glucose oxidase of pH-tunable negative charges. Both NCs are loaded into the crosslinked core of a microneedle array patch for transcutaneous delivery. The microneedle core is additionally coated with a thin sheath structure embedding H₂ O₂ -scavenging enzyme to mitigate the injury of H₂ O₂ toward normal tissues. The resulting microneedle patch can release insulin with rapid responsiveness under hyperglycemic conditions owing to an oxidative and acidic environment because of glucose oxidation, and can therefore effectively regulate blood glucose levels within a normal range on a chemically induced type 1 diabetic mouse model with enhanced biocompatibility.