Dual self-regulated delivery of insulin and glucagon by a hybrid patch

Zejun Wang; Jinqiang Wang; Hongjun Li; Jicheng Yu; Guojun Chen; Anna R Kahkoska; Valerie Wu; Yi Zeng; Di Wen; Jayson R Miedema; John B Buse; Zhen Gu

doi:10.1073/pnas.2011099117

Dual self-regulated delivery of insulin and glucagon by a hybrid patch

Proc Natl Acad Sci U S A. 2020 Nov 24;117(47):29512-29517. doi: 10.1073/pnas.2011099117. Epub 2020 Nov 11.

Authors

Zejun Wang^{1

2}, Jinqiang Wang^{1

2

3}, Hongjun Li^{1

2

3}, Jicheng Yu⁴, Guojun Chen^{1

2}, Anna R Kahkoska⁵, Valerie Wu^{1

2}, Yi Zeng^{1

2}, Di Wen^{1

2}, Jayson R Miedema^{6

7}, John B Buse⁵, Zhen Gu^{8

2

3

9}

Affiliations

¹ Department of Bioengineering, University of California, Los Angeles, CA 90095.
² California NanoSystems Institute, University of California, Los Angeles, CA 90095.
³ College of Pharmaceutical Sciences, Zhejiang University, 310058 Hangzhou, China.
⁴ Zenomics Inc., Los Angeles, CA 90095.
⁵ Department of Medicine, University of North Carolina School of Medicine, Chapel Hill, NC 27599.
⁶ Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516.
⁷ Department of Pathology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516.
⁸ Department of Bioengineering, University of California, Los Angeles, CA 90095; [email protected].
⁹ Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA 90095.

Abstract

Reduced β-cell function and insulin deficiency are hallmarks of diabetes mellitus, which is often accompanied by the malfunction of glucagon-secreting α-cells. While insulin therapy has been developed to treat insulin deficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains inadequate. Here, we describe a transdermal patch that mimics the inherent counterregulatory effects of β-cells and α-cells for blood glucose management by dynamically releasing insulin or glucagon. The two modules share a copolymerized matrix but comprise different ratios of the key monomers to be "dually responsive" to both hyper- and hypoglycemic conditions. In a type 1 diabetic mouse model, the hybrid patch effectively controls hyperglycemia while minimizing the occurrence of hypoglycemia in the setting of insulin therapy with simulated delayed meal or insulin overdose.

Keywords: glucagon delivery; glucose-responsive; hypoglycemia; insulin delivery; microneedle patch.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Blood Glucose / analysis
Blood Glucose / drug effects
Blood Glucose / metabolism
Delayed-Action Preparations / administration & dosage
Delayed-Action Preparations / chemistry
Delayed-Action Preparations / pharmacokinetics
Diabetes Mellitus, Experimental / blood
Diabetes Mellitus, Experimental / chemically induced
Diabetes Mellitus, Experimental / diagnosis
Diabetes Mellitus, Experimental / drug therapy*
Diabetes Mellitus, Type 1 / blood
Diabetes Mellitus, Type 1 / chemically induced
Diabetes Mellitus, Type 1 / diagnosis
Diabetes Mellitus, Type 1 / drug therapy*
Drug Combinations
Drug Compounding / methods
Drug Delivery Systems / methods*
Drug Liberation
Drug Overdose / prevention & control
Glucagon / administration & dosage*
Glucagon / chemistry
Glucagon / pharmacokinetics
Humans
Hypoglycemic Agents / administration & dosage*
Hypoglycemic Agents / chemistry
Hypoglycemic Agents / pharmacokinetics
Insulin / administration & dosage*
Insulin / chemistry
Insulin / pharmacokinetics
Male
Mice
Polymerization
Solubility
Streptozocin
Transdermal Patch

Substances

Blood Glucose
Delayed-Action Preparations
Drug Combinations
Hypoglycemic Agents
Insulin
Streptozocin
Glucagon

Abstract

Publication types

MeSH terms

Substances

Grants and funding