H 2 O 2-Responsive Vesicles Integrated with Transcutaneous Patches for Glucose-Mediated Insulin Delivery

ACS Nano. 2017 Jan 24;11(1):613-620. doi: 10.1021/acsnano.6b06892. Epub 2017 Jan 4.

Abstract

A self-regulated "smart" insulin administration system would be highly desirable for diabetes management. Here, a glucose-responsive insulin delivery device, which integrates H2O2-responsive polymeric vesicles (PVs) with a transcutaneous microneedle-array patch was prepared to achieve a fast response, excellent biocompatibility, and painless administration. The PVs are self-assembled from block copolymer incorporated with polyethylene glycol (PEG) and phenylboronic ester (PBE)-conjugated polyserine (designated mPEG-b-P(Ser-PBE)) and loaded with glucose oxidase (GOx) and insulin. The polymeric vesicles function as both moieties of the glucose sensing element (GOx) and the insulin release actuator to provide basal insulin release as well as promote insulin release in response to hyperglycemic states. In the current study, insulin release responds quickly to elevated glucose and its kinetics can be modulated by adjusting the concentration of GOx loaded into the microneedles. In vivo testing indicates that a single patch can regulate glucose levels effectively with reduced risk of hypoglycemia.

Keywords: diabetes; drug delivery; glucose-responsive; insulin; polymersome; vesicles.

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
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / drug therapy
  • Drug Carriers / chemical synthesis
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods*
  • Glucose / analysis
  • Glucose / metabolism*
  • Glucose Oxidase / metabolism
  • Hydrogen Peroxide / chemistry*
  • Hypoglycemia / drug therapy*
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Insulin / pharmacology
  • Kinetics
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Polymers / chemical synthesis
  • Polymers / chemistry
  • Streptozocin
  • Transdermal Patch*

Substances

  • Drug Carriers
  • Insulin
  • Polymers
  • Streptozocin
  • Hydrogen Peroxide
  • Glucose Oxidase
  • Glucose