Local inhibition of angiogenesis by halofuginone coated silicone materials

J Mater Sci Mater Med. 2012 May;23(5):1203-10. doi: 10.1007/s10856-012-4599-1. Epub 2012 Mar 16.

Abstract

Anti-angiogenic therapy is a promising approach for the treatment of increased angiogenesis in certain diseases. We aimed to investigate the local anti-angiogenic effect of silicone implants coated with Halofuginone, an angiogenesis inhibitor that inhibits synthesis of collagen-type-I and matrix metalloproteinases. The degree of angiogenesis was observed after implantation of surface modified Halofuginone eluting silicone implants into a submuscular pocket in rats over a period of 3 months. Subsequently, key mediators of angiogenesis (TGF-beta-1, bFGF, COL1A1, MMP-2, MMP-9, VEGF and PDGF) were established by immunohistological staining and RT-PCR and statistically evaluated. In comparison to uncoated silicone implants, Halofuginone eluting silicone implants lead to a significant local decrease of angiogenesis. Halofuginone eluting hybrid surface silicone implants have a significant local anti-angiogenic effect by down-regulating the expression activity of key mediators of angiogenesis.

Publication types

  • Evaluation Study

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / pharmacology*
  • Down-Regulation / drug effects
  • Drug Delivery Systems
  • Gene Expression Regulation / drug effects
  • Materials Testing
  • Models, Biological
  • Neovascularization, Physiologic / drug effects*
  • Neovascularization, Physiologic / genetics
  • Piperidines / chemistry
  • Piperidines / pharmacokinetics
  • Piperidines / pharmacology*
  • Prostheses and Implants
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacokinetics
  • Quinazolinones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Silicones / chemistry
  • Silicones / pharmacology*

Substances

  • Angiogenesis Inhibitors
  • Coated Materials, Biocompatible
  • Piperidines
  • Quinazolinones
  • Silicones
  • halofuginone