Abstract
A 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.
| Original language | English (US) |
|---|---|
| Article number | 2303665 |
| Journal | Advanced Science |
| Volume | 10 |
| Issue number | 30 |
| DOIs | |
| State | Published - Oct 26 2023 |
Funding
J.F.L and A.GN. contributed equally to the work. The work was supported in part through funding from the Leona M. and Harry B. Helmsley Charitable Trust Grant (#2109-04810) to X.Y.W and A.G., Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery (RGPIN 170460-13) and Equipment grants (EQPEQ 374799-09; EQPEQ 440689-13) to X.Y.W. The authors would also like to thank the University of Toronto Fellowship/Ben Cohen Bursary and Mitacs Accelerate Internship to J.F.L., Mitacs Accelerate Internship and NSERC CREATE scholarship to S.M., the staff of the Analytical Laboratory for Environmental Science Research (ANALEST), Centre for Research and Applications in Fluidic Technologies (CRAFT), and Microscopy Imaging Laboratory (MIL) facilities at the University of Toronto for helping with the experiments. J.F.L and A.GN. contributed equally to the work. The work was supported in part through funding from the Leona M. and Harry B. Helmsley Charitable Trust Grant (#2109‐04810) to X.Y.W and A.G., Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery (RGPIN 170460‐13) and Equipment grants (EQPEQ 374799‐09; EQPEQ 440689‐13) to X.Y.W. The authors would also like to thank the University of Toronto Fellowship/Ben Cohen Bursary and Mitacs Accelerate Internship to J.F.L., Mitacs Accelerate Internship and NSERC CREATE scholarship to S.M., the staff of the Analytical Laboratory for Environmental Science Research (ANALEST), Centre for Research and Applications in Fluidic Technologies (CRAFT), and Microscopy Imaging Laboratory (MIL) facilities at the University of Toronto for helping with the experiments.
Keywords
- diabetes treatment
- glucose-responsive hydrogel
- matrix microneedle patch
- molecular dynamics modeling
- self-crosslinking
ASJC Scopus subject areas
- Medicine (miscellaneous)
- General Chemical Engineering
- General Materials Science
- Biochemistry, Genetics and Molecular Biology (miscellaneous)
- General Engineering
- General Physics and Astronomy
