On demand regulation of blood glucose level by biocompatible oxidized starch-Con A nanogels for glucose-responsive release of exenatide

Abstract

Diabetes mellitus is a long-term chronic disease characterized by abnormal high level blood glucose (BG). An artificial closed-loop system that mimics pancreatic β-cells and releases insulin on demand has potential to improve the therapeutic efficiency of diabetes. Herein, a lectin Concanavalin A modified oxidized starch nanogel was designed to regulate glucose dynamically according to different glucose concentrations. The nanogels were formed by double cross-linking the Concanavalin A and glucose units on oxidized starch via specific binding and amide bonds to achieve the high drug loading and glucose responsiveness. The results showed that oxidized starch nanogels prolonged the half-life of antidiabetic peptide drug exenatide and released it in response to high BG concentrations. It could absorb BG at a high level and maintain glucose homeostasis. Besides, the oxidized starch nanogels performed well in recovering regular BG level from hyperglycemia state and maintaining in euglycemia state that fitted in a biological rhythm. In addition, the nanogels showed high biocompatibility in vivo and could improve plasma half-life and therapeutic efficacy of exenatide. Overall, the nanogels protected peptide drugs from degradation in plasma as a glucose-responsive platform showing a high potential for peptide drugs delivery and antidiabetic therapy.

Keywords: Antidiabetic therapy; Blood glucose homeostasis; Concanavalin A; Exenatide; Glucose-responsive delivery; Oxidized starch nanogels.