Hypoxia and H2O2 Dual-Sensitive Vesicles for Enhanced Glucose-Responsive Insulin Delivery

Nano Lett. 2017 Feb 8;17(2):733-739. doi: 10.1021/acs.nanolett.6b03848. Epub 2017 Jan 12.

Abstract

A glucose-responsive closed-loop insulin delivery system mimicking pancreas activity without long-term side effect has the potential to improve diabetic patients' health and quality of life. Here, we developed a novel glucose-responsive insulin delivery device using a painless microneedle-array patch containing insulin-loaded vesicles. Formed by self-assembly of hypoxia and H2O2 dual-sensitive diblock copolymer, the glucose-responsive polymersome-based vesicles (d-GRPs) can disassociate and subsequently release insulin triggered by H2O2 and hypoxia generated during glucose oxidation catalyzed by glucose specific enzyme. Moreover, the d-GRPs were able to eliminate the excess H2O2, which may lead to free radical-induced damage to skin tissue during the long-term usage and reduce the activity of GOx. In vivo experiments indicated that this smart insulin patch could efficiently regulate the blood glucose in the chemically induced type 1 diabetic mice for 10 h.

Keywords: Drug delivery; H2O2-sensitive; diabetes; glucose-responsive; hypoxia-sensitive; insulin.

Publication types

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

MeSH terms

  • Animals
  • Blood Glucose / metabolism
  • Cell Hypoxia
  • Diabetes Mellitus, Experimental / drug therapy
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Type 1 / drug therapy
  • Diabetes Mellitus, Type 1 / metabolism
  • Drug Carriers / chemistry*
  • Drug Liberation
  • Glucose / metabolism*
  • Glucose Oxidase / metabolism
  • HeLa Cells
  • Humans
  • Hydrogen Peroxide / metabolism*
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / chemistry
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Male
  • Mice, Inbred C57BL
  • Nitroimidazoles / chemistry
  • Oxidation-Reduction
  • Peptides / chemistry
  • Polyethylene Glycols / chemistry

Substances

  • Blood Glucose
  • Drug Carriers
  • Hypoglycemic Agents
  • Insulin
  • Nitroimidazoles
  • Peptides
  • polyserine
  • Polyethylene Glycols
  • Hydrogen Peroxide
  • Glucose Oxidase
  • Glucose