Injectable Biodegradable Polymeric Complex for Glucose-Responsive Insulin Delivery
Jinqiang Wang, Zejun Wang, Guojun Chen, Yanfang Wang, Tianyuan Ci, Hongjun Li, Xiangsheng Liu, Daojia Zhou, Anna R. Kahkoska, Zhuxian Zhou, Huan Meng, John B. Buse, Zhen Gu
Abstract
Insulin therapy is the central component of treatment for type 1 and advanced type 2 diabetes; however, its narrow therapeutic window is associated with a risk of severe hypoglycemia. A glucose-responsive carrier that demonstrates consistent and slow basal insulin release under a normoglycemic condition and accelerated insulin release in response to hyperglycemia in real-time could offer effective blood glucose regulation with reduced risk of hypoglycemia. Here, we describe a poly(l-lysine)-derived biodegradable glucose-responsive cationic polymer for constructing polymer-insulin complexes for glucose-stimulated insulin delivery. The effects of the modification degree of arylboronic acid in the synthesized cationic polymer and polymer-to-insulin ratio on the glucose-dependent equilibrated free insulin level and the associated insulin release kinetics have been studied. In addition, the blood glucose regulation ability of these complexes and the associated glucose challenge-triggered insulin release are evaluated in type 1 diabetic mice.