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Nano Research

Article Title

Glucose-responsive oral insulin delivery for postprandial glycemic regulation

Authors

Jicheng Yu, Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA
Yuqi Zhang, Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA
Jinqiang Wang, Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Di Wen, Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA
Anna R. Kahkoska, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
John B. Buse, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
Zhen Gu, Joint Department of Biomedical Engineering, University of North Carolina at Chapel Hill and North Carolina State University, Raleigh, NC 27695, USA Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA 90095, USA Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA California NanoSystems Institute (CNSI), Jonsson Comprehensive Cancer Center, Center for Minimally Invasive Therapeutics University of California, Los Angeles, Los Angeles, CA 90095, USA

Keywords

diabetes, drug delivery, glucose-responsive, insulin, nanomedicine

Abstract

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.

Graphical Abstract

Publisher

Tsinghua University Press

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