Glucose- and H₂O₂-Responsive Polymeric Vesicles Integrated with Microneedle Patches for Glucose-Sensitive Transcutaneous Delivery of Insulin in Diabetic Rats

Abstract

Herein, a dual-responsive insulin delivery device by integrating glucose- and H₂O₂-responsive polymeric vesicles (PVs) with transcutaneous microneedles (MNs) has been designed. This novel microneedle delivery device achieves a goal of fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from a triblock copolymer including poly(ethylene glycol), poly(phenylboronic acid) (glucose-sensitive block), and poly(phenylboronic acid pinacol ester) (H₂O₂-sensitive block). After loading with insulin and glucose oxidase (GO _x), the drug-loaded PVs display a basal insulin release as well as a promoted insulin release in response to hyperglycemic states. The insulin release rate responds quickly to elevated glucose and can be further promoted by the incorporated GO _x, which will generate the H₂O₂ at high glucose levels and further break the chemical links of phenylboronic acid pinacol ester group. Finally, the transdermal delivery of insulin to the diabetic rats ((insulin + GO _x)-loaded MNs) presents an effective hypoglycemic effect compared to that of subcutaneous injection or only insulin-loaded MNs, which indicates the as-prepared MNs insulin delivery system could be of great importance for the applications in the therapy of diabetes.