Glucose-Responsive Composite Microneedle Patch for Hypoglycemia-Triggered Delivery of Native Glucagon

Amin GhavamiNejad, Jason Li, Brian Lu, Liwei Zhou, Loretta Lam, Adria Giacca, Xiao Yu Wu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Insulin-dependent patients with diabetes mellitus require multiple daily injections of exogenous insulin to combat hyperglycemia. However, administration of excess insulin can lead to hypoglycemia, a life-threatening condition characterized by abnormally low blood glucose levels (BGLs). To prevent hypoglycemia associated with intensive insulin therapy, a “smart” composite microneedle (cMN) patch is developed, which releases native glucagon at low glucose levels. The cMN patch is composed of a photo-crosslinked methacrylated hyaluronic acid (MeHA) microneedle array with embedded multifunctional microgels. The microgels incorporate zwitterionic moieties that stabilize loaded glucagon and phenylboronic acid moieties that provide glucose-dependent volume change to facilitate glucagon release. Hypoglycemia-triggered release of structurally unchanged glucagon from the cMN patch is demonstrated in vitro and in a rat model of type 1 diabetes (T1D). Transdermal application of the patch prevented insulin-induced hypoglycemia in the diabetic rats. This work is the first demonstration of a glucose-responsive glucagon-delivery MN patch for the prevention of hypoglycemia, which has a tremendous potential to reduce the dangers of intensive insulin therapy and improve the quality of life of patients with diabetes and their caregivers.

Original languageEnglish (US)
Article number1901051
JournalAdvanced Materials
Volume31
Issue number30
DOIs
StatePublished - Jul 26 2019

Keywords

  • composite microneedle patches
  • diabetes
  • glucagon delivery
  • glucose-responsive microgels
  • hypoglycemia prevention

ASJC Scopus subject areas

  • Mechanics of Materials
  • Mechanical Engineering
  • General Materials Science

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