Glucose-responsive UV polymerised dextran-concanavalin A acrylic derivatised mixtures for closed-loop insulin delivery

Biomaterials. 2006 Mar;27(8):1586-97. doi: 10.1016/j.biomaterials.2005.08.011. Epub 2005 Sep 2.

Abstract

A novel UV polymerised glucose-responsive mixture containing concanavalin A (con A) and dextran was synthesised and characterised as a "smart" biomaterial to form the basis of a closed-loop delivery device. Dextran and con A precursors were modified with acrylic side groups and then UV polymerised to produce covalently bonded mixtures which were examined by FTIR. The viscoelastic properties of these polymerised mixtures containing glucose concentrations between 0% and 5% w/w were also examined using oscillatory rheometry within the linear viscoelastic range across a frequency range of 0.01-50 Hz. As the formulation glucose concentration was raised, a graded decrease in storage modulus, loss modulus and complex viscosity when compared at 1 Hz was observed. Increasing the mixture irradiation time produced viscosity profiles at higher values throughout the glucose concentration range. The subsequent testing of such formulations in in vitro diffusion experiments revealed that the leaching of the mixture components is formulation dependent and is restricted significantly in the covalently bonded mixtures. Insulin delivery in response to glucose in the physiologically relevant glucose concentration range was demonstrated using the novel polymerised mixture at 37 degrees C. The performance of this covalently cross-linked glucose-responsive biomaterial has been improved in terms of increased mixture stability with reduced component leaching. This could, therefore be used as the basis of the design of a closed-loop drug delivery device for therapeutic agents used for the management of diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrylic Resins* / chemistry
  • Biocompatible Materials* / chemistry
  • Concanavalin A*
  • Dextrans* / chemistry
  • Diffusion
  • Drug Delivery Systems*
  • Glucose
  • Insulin / administration & dosage*
  • Rheology
  • Spectroscopy, Fourier Transform Infrared
  • Temperature
  • Ultraviolet Rays*

Substances

  • Acrylic Resins
  • Biocompatible Materials
  • Dextrans
  • Insulin
  • Concanavalin A
  • Glucose