Microneedles Integrated with ZnO Quantum-Dot-Capped Mesoporous Bioactive Glasses for Glucose-Mediated Insulin Delivery

A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GO_<i>x</i>/CAT) were sealed into the pores of MBGs. GO_<i>x</i>/CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes

Separable Microneedles for Near-Infrared Light-Triggered Transdermal Delivery of Metformin in Diabetic Rats

Near-infrared (NIR) light-triggered and separable segmented microneedles (MNs), consisting of lauric acid and polycaprolactone (LA/PCL) arrowheads and poly­(vinyl alcohol) and polycaprolactone (PVA/PVP) supporting bases, have been fabricated. A hypoglycemic drug (metformin) and photothermal conversion factor (Cu₇S₄ nanoparticles) are encapsulated into LA/PCL arrowheads. Due to the dissolution of soluble supporting bases after the absorption of tissue fluid, the separable MNs arrowheads can be embedded into skin after insertion. Under the NIR-light irradiation, the LA/PCL arrowheads exhibit an excellent thermal-ablation change with a low amount of Cu₇S₄ nanoparticles (0.1 wt %) due to the low melting point of LA and PCL, thus enabling the release behavior of the encapsulated model drug to be photothermally triggered. Compared to the hypodermic injection of metformin, the thermal ablation of separable MNs triggered by NIR irradiation in the current research exhibit an excellent hypoglycemic effect in vivo. It suggests that the NIR-induced thermal-ablation MNs comprise a prospective transdermal drug-delivery system for the precise control of the timing and dosage of a drug that is dependent on NIR administration