Glucose-Responsive Nanoparticles for Targeted Insulin Delivery in the Treatment of Diabetes

Abstract

Diabetes mellitus (DM) is one of the most common metabolic disorders worldwide, which is manifested by chronic hyperglycemia due to defects in insulin secretion or action. Conventional insulin therapy is compromised by variable glycemic control, hypoglycemic risk and patient non-compliance associated with high number of injections. To address these issues, glucose-responsive nanoparticles (GR-NPs) have become an attractive approach for intelligent insulin delivery. The glucose-responsive nanosystems can monitor the fluctuant physiological glucose concentration and release the insulin under feedback control, similar to the pancreatic β-cell behavior. In this report, phenylboronic acid-modified polymers and chitosan-based carriers are used to prepare glucose-responsive nanoparticles, and their engineering design, synthesis and properties are investigated. In vitro profiling showed over 80% of encapsulation efficiency and sustained glucose-stimulated insulin release when exposed to glucose concentrations ≥200 mg/dL. Cytocompatibility tests of pancreatic β-cell lines did not reveal any toxicity. In addition, in vivo-like simulations forecasted a better glycemic control and a lower hypoglycemia risk than subcutaneous needle injections. We conclude that GR-NPs exhibit great promise as the next generation of platforms for accurate, user-friendly treatment of diabetes.