Affiliation:
1. Advanced Pharmaceutics and Drug Delivery Laboratory Leslie L. Dan Faculty of Pharmacy University of Toronto Toronto M5S 3M2 Canada
2. Department of Physiology Faculty of Medicine University of Toronto Toronto M5S 1A8 Canada
Abstract
AbstractA transdermal patch that delivers insulin at high glucose concentrations can offer tremendous advantages to ease the concern of safety and improve the quality of life for people with diabetes. Herein, a novel self‐crosslinkable and glucose‐responsive polymer‐based microneedle patch (MN) is designed to deliver insulin at hyperglycemia. The microneedle patch is made of hyaluronic acid polymers functionalized with dopamine and 4‐amino‐3‐fluorophenylboronic acid (AFBA) that can be quickly crosslinked upon mixing of the polymer solutions in the absence of any chemicalcrosslinking agents or organic solvents. The catechol groups in the dopamine (DA) units form covalent crosslinkages among themselves by auto‐oxidation and dynamic crosslink with phenylboronic acid (PBA) via complexation. The reversible crosslinkages between catechol and boronate decrease with increasing glucose concentration leading to higher swelling and faster insulin release at hyperglycemia as compared to euglycemia. Such superior glucose‐responsive properties are demonstrated by in vitro analyses and in vivo efficacy studies. The hydrogel polymers also preserve native structure and bioactivity of insulin, attributable to the interaction of hyaluronic acid (HA) with insulin molecules, as revealed by experiments and molecular dynamics simulations. The simplicity in the design and fabrication process, and glucose‐responsiveness in insulin delivery impart the matrix microneedle (mMN) patch great potential for clinical translation.
Funder
Leona M. and Harry B. Helmsley Charitable Trust
Subject
General Physics and Astronomy,General Engineering,Biochemistry, Genetics and Molecular Biology (miscellaneous),General Materials Science,General Chemical Engineering,Medicine (miscellaneous)
Cited by
3 articles.
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