Glucose-responsive oral insulin delivery for postprandial glycemic regulation
Controlling postprandial glucose levels for diabetic patients is critical to achieve the tight glycemic control that decreases the risk for developing long-term micro- and macrovascular complications. Herein, we report a glucose-responsive oral insulin delivery system based on Fc receptor (FcRn)-targeted liposomes with glucose-sensitive hyaluronic acid (HA) shell for postprandial glycemic regulation. After oral administration, the HA shell can quickly detach in the presence of increasing intestinal glucose concentration due to the competitive binding of glucose with the phenylboronic acid groups conjugated with HA. The exposed Fc groups on the surface of liposomes then facilitate enhanced intestinal absorption in an FcRn-mediated transport pathway. In vivo studies on chemically-induced type 1 diabetic mice show this oral glucose-responsive delivery approach can effectively reduce postprandial blood glucose excursions. This work is the first demonstration of an oral insulin delivery system directly triggered by increasing postprandial glucose concentrations in the intestine to provide an on-demand insulin release with ease of administration.
Keywordsdiabetes drug delivery glucose-responsive insulin nanomedicine
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This work was supported by the grants from NC TraCS, NIH’s Clinical and Translational Science Awards (CTSA, NIH grant 1UL1TR001111) at UNC-CH and Sloan Research Fellowship. We acknowledge the use of the Analytical Instrumentation Facility (AIF) at NC State, which is supported by the State of North Carolina and the National Science Foundation (NSF).
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