Biomimetic Glucose Trigger‐Insulin Release System Based on Hydrogel Loading Bidentate β‐Cyclodextrin

Abstract

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 β-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 β-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 β-CD hydrogel is preloaded with short-activity insulin, it exerts long-activity control of blood glucose level over 12 h.

Hydrogels and Hydrogel Nanocomposites: Enhancing Healthcare through Human and Environmental Treatment

“…developed a biomimetic glucose trigger‐insulin release hydrogel system based on a bidentate‐ β ‐cyclodextrin preloaded with insulin. [ 215 ] The dual self‐regulated hydrogel showed specific binding between d ‐glucose and bidentate‐ β ‐cyclodextrin and exhibited macroscopic swelling due to proton release. While hydrogel expansion triggered release of preloaded insulin, isomers of d ‐glucose caused shrinkage and therefore delayed the release of insulin, enabling steady and prolonged blood glucose control (12+ h).…”

Cyclodextrin-Modified Nanomaterials for Drug Delivery: Classification and Advances in Controlled Release and Bioavailability

“…On the other hand, a smart stimulus, such as specific biomolecules overexpression, is also used to trigger drug release. For example, this can be seen in studies such as those reported by Wang et al [8] and Xu et al, in which modified βCD-loading insulin triggered release in the presence of high glucose concentrations [166,167]. In both studies, the formulations were demonstrated to be safe and specific glucose-responsive drug carriers with potential use for the therapy of diabetes.…”

Biomimetic Biomaterials Based on Polysaccharides: Recent Progress and Future Perspectives

“…[ 169,198 ] A bidentate β ‐CD‐based hydrogel was preloaded with insulin to produce a dual d ‐glucose‐sensitive self‐regulated system. [ 199 ] The excellent potential to accurately monitor glucose levels and trigger insulin release was made possible by associating the CD with phenylboronic acid since CDs themselves or their direct derivatives are not selective toward d ‐glucose. An alternative glucose biosensor was also recently reported, based on β ‐CDs grafted onto magnetite/polydopamine with adsorbed glucose oxidase from Aspergillus niger .…”