Biomimetic Glucose Trigger-Insulin Release System Based On Hydrogel Loading Bidentate Beta-Cyclodextrin

Initiated by the specific binding between D-glucose and biological receptors, the human body has a delicate metabolic system to regulate blood D-glucose levels, but failing to release insulin would induce hyperglycemia or type I diabetes. While insulin delivery is an effective form of hyperglycemia therapy, the self-regulated triggering of insulin release for on-demand supplementation remains inadequate. Here, a biomimetic glucose trigger-insulin release system, that is, a bidentate beta-cyclodextrin-based hydrogel with preloaded insulin is presented; the dual self-regulated system shows a specific D-glucose response to realize accurate monitoring and simultaneous on-demand trigger insulin release. The specific binding between D-glucose and the bidentate beta-cyclodextrin induces the release of protons, causing macroscopic swelling of the hydrogel, subsequently triggering the on-demand and long-term supplementation of insulin. On the contrary, isomers of D-glucose, such as D-fructose and D-galactose, cause shrinking of the hydrogel, and retard insulin release. In-vivo studies in type I diabetic mice model ascertain that although the bidentate beta-CD hydrogel is preloaded with short-activity insulin, it exerts long-activity control of blood glucose level over 12 h.