“Smart” Matrix Microneedle Patch Made of Self-Crosslinkable and Multifunctional Polymers for Delivering Insulin On-Demand

Jackie Fule Liu, Amin GhavamiNejad, Brian Lu, Sako Mirzaie, Melisa Samarikhalaj, Adria Giacca, Xiao Yu Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

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 languageEnglish (US)
Article number2303665
JournalAdvanced Science
Volume10
Issue number30
DOIs
StatePublished - Oct 26 2023

Keywords

  • diabetes treatment
  • glucose-responsive hydrogel
  • matrix microneedle patch
  • molecular dynamics modeling
  • self-crosslinking

ASJC Scopus subject areas

  • General Engineering
  • General Chemical Engineering
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Materials Science
  • General Physics and Astronomy
  • Medicine (miscellaneous)

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