Core-Shell Microneedle Gel for Self-Regulated Insulin Delivery

ACS Nano. 2018 Mar 27;12(3):2466-2473. doi: 10.1021/acsnano.7b08152. Epub 2018 Feb 19.

Abstract

A bioinspired glucose-responsive insulin delivery system for self-regulation of blood glucose levels is desirable for improving health and quality of life outcomes for patients with type 1 and advanced type 2 diabetes. Here we describe a painless core-shell microneedle array patch consisting of degradable cross-linked gel for smart insulin delivery with rapid responsiveness and excellent biocompatibility. This gel-based device can partially dissociate and subsequently release insulin when triggered by hydrogen peroxide (H2O2) generated during the oxidation of glucose by a glucose-specific enzyme covalently attached inside the gel. Importantly, the H2O2-responsive microneedles are coated with a thin-layer embedding H2O2-scavenging enzyme, thus mimicking the complementary function of enzymes in peroxisomes to protect normal tissues from injury caused by oxidative stress. Utilizing a chemically induced type 1 diabetic mouse model, we demonstrated that this smart insulin patch with a bioresponsive core and protective shell could effectively regulate the blood glucose levels within a normal range with improved biocompatibility.

Keywords: diabetes; drug delivery; hydrogel; microneedle; stimuli-responsive.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Blood Glucose / analysis
  • Blood Glucose / metabolism
  • Delayed-Action Preparations / metabolism*
  • Diabetes Mellitus, Type 1 / blood
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Diabetes Mellitus, Type 1 / metabolism
  • Drug Delivery Systems / instrumentation*
  • Enzymes, Immobilized / metabolism
  • Equipment Design
  • Humans
  • Hydrogels / metabolism*
  • Hydrogen Peroxide / metabolism*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / therapeutic use
  • Insulin / administration & dosage*
  • Insulin / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Needles
  • Transdermal Patch

Substances

  • Blood Glucose
  • Delayed-Action Preparations
  • Enzymes, Immobilized
  • Hydrogels
  • Hypoglycemic Agents
  • Insulin
  • Hydrogen Peroxide