Injectable nano-network for glucose-mediated insulin delivery

ACS Nano. 2013 May 28;7(5):4194-201. doi: 10.1021/nn400630x. Epub 2013 May 2.


Diabetes mellitus, a disorder of glucose regulation, is a global burden affecting 366 million people across the world. An artificial "closed-loop" system able to mimic pancreas activity and release insulin in response to glucose level changes has the potential to improve patient compliance and health. Herein we develop a glucose-mediated release strategy for the self-regulated delivery of insulin using an injectable and acid-degradable polymeric network. Formed by electrostatic interaction between oppositely charged dextran nanoparticles loaded with insulin and glucose-specific enzymes, the nanocomposite-based porous architecture can be dissociated and subsequently release insulin in a hyperglycemic state through the catalytic conversion of glucose into gluconic acid. In vitro insulin release can be modulated in a pulsatile profile in response to glucose concentrations. In vivo studies validated that these formulations provided improved glucose control in type 1 diabetic mice subcutaneously administered with a degradable nano-network. A single injection of the developed nano-network facilitated stabilization of the blood glucose levels in the normoglycemic state (<200 mg/dL) for up to 10 days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry
  • Animals
  • Biocompatible Materials / administration & dosage
  • Biocompatible Materials / chemistry
  • Chitosan / chemistry
  • Dextrans / chemistry
  • Diabetes Mellitus, Type 1 / drug therapy
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemistry*
  • Glucose / metabolism*
  • Glucuronic Acid / chemistry
  • Hexuronic Acids / chemistry
  • Humans
  • Injections
  • Insulin / chemistry
  • Insulin / metabolism*
  • Insulin / therapeutic use
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nanoparticles / administration & dosage*
  • Nanoparticles / chemistry*


  • Alginates
  • Biocompatible Materials
  • Dextrans
  • Drug Carriers
  • Hexuronic Acids
  • Insulin
  • Glucuronic Acid
  • Chitosan
  • Glucose