Glucose-Responsive Gold Nanocluster-Loaded Microneedle Patch for Type 1 Diabetes Therapy.

Responsive blood glucose control in a convenient and noninvasive manner is the ultimate goal in diabetes treatment. In this study, we developed a closed-loop microneedle (MN)-array patch for transdermal and responsive insulin delivery in type 1 diabetes therapy. We prepared alginate-based MN-array patches integrated with glucose-responsive gold nanoclusters (GNCs) using a two-step casting and centrifuging process. From both theoretical calculation and experimental study, we found that the integration of GNCs into MNs significantly improved the mechanical strength of alginate-based MN-array patches. The GNCs facilitated the MNs to penetrate the skin of mice, and the glucose-responsive GNCs in MNs allowed the closed-loop insulin release both in vitro in glucose solutions and in vivo in type 1 diabetic mice. With transdermal application only once on the skin of mice, the MN-array patches regulated the blood glucose levels of mice in normoglycemic ranges for up to 2.8 days and decreased the diabetic symptoms of the mice. Our study proved the successful application of glucose-responsive GNC-loaded MN-array patches for minimally invasive and responsive insulin delivery, providing a promising alternative for type 1 diabetes therapy.