Research ArticleHEALTH AND MEDICINE

Charge-switchable polymeric complex for glucose-responsive insulin delivery in mice and pigs

See allHide authors and affiliations

Science Advances  10 Jul 2019:
Vol. 5, no. 7, eaaw4357
DOI: 10.1126/sciadv.aaw4357

Abstract

Glucose-responsive insulin delivery systems with robust responsiveness that has been validated in animal models, especially in large animal models, remain elusive. Here, we exploit a new strategy to form a micro-sized complex between a charge-switchable polymer with a glucose-sensing moiety and insulin driven by electrostatic interaction. Both high insulin loading efficiency (95%) and loading capacity (49%) can be achieved. In the presence of a hyperglycemic state, the glucose-responsive phenylboronic acid (PBA) binds glucose instantly and converts the charge of the polymeric moiety from positive to negative, thereby enabling the release of insulin from the complex. Adjusting the ratio of the positively charged group to PBA achieves inhibited insulin release from the complex under normoglycemic conditions and promoted release under hyperglycemic conditions. Through chemically induced type 1 diabetic mouse and swine models, in vivo hyperglycemia-triggered insulin release with fast response is demonstrated after the complex is administrated by either subcutaneous injection or transdermal microneedle array patch.

This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

View Full Text