Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.
Injectable Nano-Network for Glucose-Mediated Insulin Delivery
Creators
Zhen Gu - Massachusetts Institute of Technology
Alex A. Aimetti - Massachusetts Institute of Technology
Qun Wang - Massachusetts Institute of Technology
Tram T. Dang - Massachusetts Institute of Technology
Yunlong Zhang - Massachusetts Institute of Technology
Omid Veiseh - Massachusetts Institute of Technology
Hao Cheng - Drexel University
Robert S. Langer - Massachusetts Institute of Technology
Daniel G. Anderson - Massachusetts Institute of Technology
Publication Details
ACS nano, v 7(5), pp 4194-4201
Publisher
American Chemical Society; Washington, DC
Number of pages
8
Grant note
09PG-T1D027 / Leona M. and Harry B. Helmsley Charitable Trust Foundation
P30CA014051 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
Resource Type
Journal article
Language
English
Academic Unit
Materials Science and Engineering
Web of Science ID
WOS:000319856300056
Scopus ID
2-s2.0-84878339119
Other Identifier
991019169798004721
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Collaboration types
Domestic collaboration
Web of Science research areas
Chemistry, Multidisciplinary
Chemistry, Physical
Materials Science, Multidisciplinary
Nanoscience & Nanotechnology
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