Heparin-functionalized chitosan-alginate scaffolds for controlled release of growth factor

Int J Pharm. 2009 Jul 6;376(1-2):69-75. doi: 10.1016/j.ijpharm.2009.04.048. Epub 2009 May 18.

Abstract

Controlled long-term release of basic fibroblast growth factor (bFGF) has shown a combined effect on the stimulation of regenerating a number of tissues including cartilage, nerve, skin and liver. In this study, three-dimensional scaffolds prepared from the polyelectrolyte complexes (PEC) of chitosan and alginate were developed for the delivery of bFGF. The bFGF-binding efficiency of the chitosan-alginate PEC scaffold, after being conjugated with high concentration of heparin (83.6 microg/mg scaffold), was increased up to 15 times higher than that of original scaffold (65.6 ng bFGF/mg scaffold vs. 4.5 ng bFGF/mg scaffold). The release of bFGF from the original scaffold was quick and the initial burst release was obvious. By functionalizing the scaffold with various concentrations of heparin (17.6 microg, 50.3 microg and 83.6 microg heparin/mg scaffold), the rate of bFGF release from the scaffold decreased in a controlled manner with reduced burst effect. The released bFGF retained its biological activity as assessed by the in vitro proliferation of human foreskin fibroblast (HFF). This study shows that a novel bFGF delivery system using the heparin-functionalized chitosan-alginate PEC scaffold exhibits controllable, long-term release of bFGF and could prevent the growth factor from inactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / chemistry*
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chitosan / chemistry*
  • Delayed-Action Preparations / administration & dosage*
  • Delayed-Action Preparations / chemical synthesis
  • Drug Carriers / administration & dosage*
  • Drug Carriers / chemical synthesis
  • Fibroblast Growth Factor 2 / administration & dosage*
  • Fibroblast Growth Factor 2 / pharmacokinetics
  • Fibroblast Growth Factor 2 / pharmacology
  • Fibroblasts / drug effects
  • Foreskin / drug effects
  • Gels / administration & dosage
  • Gels / chemical synthesis
  • Glucuronic Acid / chemistry
  • Heparin / chemistry*
  • Hexuronic Acids / chemistry
  • Humans
  • Male

Substances

  • Alginates
  • Delayed-Action Preparations
  • Drug Carriers
  • Gels
  • Hexuronic Acids
  • Fibroblast Growth Factor 2
  • Glucuronic Acid
  • Heparin
  • Chitosan