Author:
Yu Jicheng,Zhang Yuqi,Ye Yanqi,DiSanto Rocco,Sun Wujin,Ranson Davis,Ligler Frances S.,Buse John B.,Gu Zhen
Abstract
A glucose-responsive “closed-loop” insulin delivery system mimicking the function of pancreatic cells has tremendous potential to improve quality of life and health in diabetics. Here, we report a novel glucose-responsive insulin delivery device using a painless microneedle-array patch (“smart insulin patch”) containing glucose-responsive vesicles (GRVs; with an average diameter of 118 nm), which are loaded with insulin and glucose oxidase (GOx) enzyme. The GRVs are self-assembled from hypoxia-sensitive hyaluronic acid (HS-HA) conjugated with 2-nitroimidazole (NI), a hydrophobic component that can be converted to hydrophilic 2-aminoimidazoles through bioreduction under hypoxic conditions. The local hypoxic microenvironment caused by the enzymatic oxidation of glucose in the hyperglycemic state promotes the reduction of HS-HA, which rapidly triggers the dissociation of vesicles and subsequent release of insulin. The smart insulin patch effectively regulated the blood glucose in a mouse model of chemically induced type 1 diabetes. The described work is the first demonstration, to our knowledge, of a synthetic glucose-responsive device using a hypoxia trigger for regulation of insulin release. The faster responsiveness of this approach holds promise in avoiding hyperglycemia and hypoglycemia if translated for human therapy.
Funder
The American Diabetes Association Research Foundation
HHS | National Institutes of Health
Publisher
Proceedings of the National Academy of Sciences
Cited by
650 articles.
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