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 language | English (US) |
|---|---|
| Article number | 1901051 |
| Journal | Advanced Materials |
| Volume | 31 |
| Issue number | 30 |
| DOIs | |
| State | Published - Jul 26 2019 |
Funding
A.GN., J.L., and B.L. contributed equally to this work. This research was supported by the grant from JDRF (2-SRA-2016-268-A-N) to X.Y.W. and A.G., and 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 OGS scholarship to B.L., BBDC Seller Fellowship to A.GN., the staff of the ANALEST at the University of Toronto for help with analytical experiments. All conducted in vivo animal studies strictly followed the ethical and legal requirements of the Ontario Animals for Research Act and the Federal Canadian Council on Animal Care guidelines, and were approved by the University Animal Care Committee of the University of Toronto.
Keywords
- composite microneedle patches
- diabetes
- glucagon delivery
- glucose-responsive microgels
- hypoglycemia prevention
ASJC Scopus subject areas
- General Materials Science
- Mechanics of Materials
- Mechanical Engineering
