Journal Article

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

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

2020

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Animals / Applied Biological Sciences / Beta cells / Biological Sciences / Blood glucose / Blood Glucose - analysis / Blood Glucose - drug effects / Blood Glucose - metabolism / Copolymerization / Delayed-Action Preparations - administration & dosage / Delayed-Action Preparations - chemistry / Delayed-Action Preparations - pharmacokinetics / Diabetes mellitus / 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 / Engineering / Glucagon / Glucagon - administration & dosage / Glucagon - chemistry / Glucagon - pharmacokinetics / Humans / Hyperglycemia / Hypoglycemia / Hypoglycemic Agents - administration & dosage / Hypoglycemic Agents - chemistry / Hypoglycemic Agents - pharmacokinetics / Insulin / Insulin - administration & dosage / Insulin - chemistry / Insulin - pharmacokinetics / Male / Mice / Monomers / Overdose / Physical Sciences / Polymerization / Solubility / Streptozocin / Supplements / Transdermal Patch