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

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.

• Authors: Amin GhavamiNejad, Jason Li, Brian Lu, Liwei Zhou, Loretta Lam, Adria Giacca, Xiao Yu Wu
• Journal: Advanced materials (Deerfield Beach, Fla.) (Adv Mater) Vol. 31 Issue 30 Pg. e1901051 (Jul 2019) ISSN: 1521-4095 [Electronic] Germany
• PMID: 31165524 (Publication Type: Journal Article)
• Copyright: © 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Blood Glucose
• Cross-Linking Reagents
• Gels
• Hypoglycemic Agents
• Insulin
• Methacrylates
• Hyaluronic Acid
• Glucagon

Topics

• Animals
• Blood Glucose (metabolism)
• Cross-Linking Reagents (chemistry)
• Diabetes Mellitus, Experimental (drug therapy, metabolism)
• Diabetes Mellitus, Type 1 (drug therapy, metabolism)
• Drug Liberation
• Gels
• Glucagon (administration & dosage)
• Humans
• Hyaluronic Acid (analogs & derivatives, chemistry)
• Hypoglycemia (chemically induced, drug therapy)
• Hypoglycemic Agents (adverse effects)
• Insulin (adverse effects)
• Methacrylates (chemistry)
• Needles
• Photochemical Processes
• Polymerization
• Rats
• Transdermal Patch