Perivascular sirolimus-delivery system

Int J Pharm. 2011 Feb 14;404(1-2):94-101. doi: 10.1016/j.ijpharm.2010.11.005. Epub 2010 Nov 12.

Abstract

Autologous vein grafts are often used for treating damaged vessels, e.g. arteriovenous fistulas or arterial bypass conduits. Veins have a different histological structure from arteries, which often leads to intimal hyperplasia and graft restenosis. The aim of this study was to develop a perivascular sirolimus-delivery system that would release the antiproliferative drug sirolimus in a controlled manner. Polyester Mesh I was coated with purasorb, i.e. a copolymer of L-lactide and ɛ-caprolactone, with dissolved sirolimus; Mesh II was coated with two copolymer layers; the layer with dissolved sirolimus was overlaid with pure purasorb. This arrangement allowed sirolimus to be released for 6 and 4 weeks, for Mesh I and Mesh II, respectively. Mesh II released sirolimus more homogeneously, without the initial burst effect during the first week. However, the cumulative release curve was steeper at later time points than the curve for Mesh I. Both meshes inhibited proliferation of rat vascular smooth muscle cells during 14-day culture in vitro and preserved excellent cell viability. Newly developed sirolimus-releasing perivascular meshes are promising devices for preventing autologous graft restenosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cardiovascular Agents / administration & dosage
  • Cardiovascular Agents / chemistry*
  • Cardiovascular Agents / pharmacology
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Chemistry, Pharmaceutical
  • Chromatography, High Pressure Liquid
  • Coated Materials, Biocompatible*
  • Delayed-Action Preparations
  • Drug Carriers*
  • Drug Compounding
  • Drug Stability
  • Graft Occlusion, Vascular / prevention & control
  • Kinetics
  • Male
  • Microscopy, Electron, Scanning
  • Molecular Weight
  • Muscle, Smooth, Vascular / drug effects
  • Myocytes, Smooth Muscle / drug effects
  • Polyesters / chemistry*
  • Rats
  • Rats, Wistar
  • Sirolimus / administration & dosage
  • Sirolimus / chemistry*
  • Sirolimus / pharmacology
  • Solubility
  • Surface Properties
  • Technology, Pharmaceutical / methods

Substances

  • Cardiovascular Agents
  • Coated Materials, Biocompatible
  • Delayed-Action Preparations
  • Drug Carriers
  • Polyesters
  • lactide-caprolactone copolymer
  • Sirolimus