Dual self-regulated delivery of insulin and glucagon by a hybrid patch
Zejun Wang, Jinqiang Wang, Hongjun Li, Jicheng Yu, Guojun Chen, Anna R. Kahkoska, Valerie Wu, Yi Zeng, Di Wen, Jayson Miedema, John B. Buse, Zhen Gu
Abstract
Reduced β-cell function and insulin deficiency are hallmarks of diabetes mellitus, which is often accompanied by the malfunction of glucagon-secreting α-cells. While insulin therapy has been developed to treat insulin deficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains inadequate. Here, we describe a transdermal patch that mimics the inherent counterregulatory effects of β-cells and α-cells for blood glucose management by dynamically releasing insulin or glucagon. The two modules share a copolymerized matrix but comprise different ratios of the key monomers to be "dually responsive" to both hyper- and hypoglycemic conditions. In a type 1 diabetic mouse model, the hybrid patch effectively controls hyperglycemia while minimizing the occurrence of hypoglycemia in the setting of insulin therapy with simulated delayed meal or insulin overdose.