Dynamically capped hierarchically porous microneedles enable post-fabrication loading and self-regulated transdermal delivery of insulin

Abstract

Glucose-responsive microneedle (MN) patches are of great interest for painless self-regulated insulin delivery in diabetic patients to improve their quality of life. This work is aimed to develop a smart MN-based insulin delivery system with potential for post-fabrication loading of insulin and a fast, repeatable response to glucose fluctuations without sacrificing its structural constituents. A hierarchically porous inorganic MN array is developed, consisting of a macroporous alumina core to provide an external access and a large capacity for insulin loading and a mesoporous shell to control insulin release by glucose-responsive gating of its nanopores that are dynamically capped with an enzyme-loaded chitosan (CS) hydrogel. The capped MNs doff their caps to blood sugar quickly and reversibly via swelling/deswelling of the CS cap. As a result, insulin release can be repeatedly regulated during sequential cycles of hyperglycemia/normoglycemia with short intervals of 40 min. In a type 1 diabetic mouse model, application of the smart MN system quickly causes normoglycemia within 1 h, which is prolonged for 5 h. Diabetic mice treated by the smart MN system behave similarly to the healthy mice in terms of controlled blood glucose levels during the in vivo glucose tolerance test. The “cap doffing” approach can aid the development of more safe, long-lasting MN systems for smart transdermal delivery of insulin and other drugs.