Nanoparticle-eluting stents for coronary intervention: formulation, characterization, and in vitro evaluation

Can J Physiol Pharmacol. 2022 Mar;100(3):220-233. doi: 10.1139/cjpp-2021-0245. Epub 2021 Sep 27.

Abstract

Coronary artery disease (CAD) is currently a leading cause of death worldwide. In the history of percutaneous coronary intervention for the treatment of CAD, a drug-eluting stent (DES) is recognized as a revolutionary technology that has the unique ability to significantly reduce restenosis and provide both mechanical and biological solutions simultaneously to the target lesion. The aim of the research work was to design and fabricate DES coated with a nanoparticulate drug formulation. Sirolimus, an inhibitor of the smooth muscle cell (SMC) proliferation and migration, was encapsulated in polymeric nanoparticles (NPs). The NP formulation was characterized for various physicochemical parameters. Cell viability and cell uptake studies were performed using human coronary artery smooth muscle cells (HCASMCs). The developed NP formulation showed enhanced efficacy compared to plain drug solution and exhibited time-dependent uptake into the HCASMCs. The developed NP formulation was coated on the Flexinnium™ ultra-thin cobalt-chromium alloy coronary stent platform. The NP-coated stents were characterized for morphology and residual solvent analysis. In vitro drug release was also evaluated. Ex vivo arterial permeation was carried out to evaluate the NP uptake from the surface of the stents. The characterization studies together corroborated that the developed NP coated stent can be a promising replacement of the current DESs.

Keywords: cellules musculaires lisses d’artères coronaires humaines; coronaropathie; coronary artery disease; drug-eluting stents; endoprothèses à élution de médicaments; human coronary artery smooth muscle cells; nanoparticles; nanoparticules; restenosis; resténose; sirolimus.

MeSH terms

  • Cell Survival / drug effects
  • Cells, Cultured
  • Chemical Phenomena
  • Chromium Alloys
  • Coronary Vessels / cytology
  • Coronary Vessels / metabolism
  • Drug Compounding / methods*
  • Drug Liberation*
  • Drug-Eluting Stents*
  • Humans
  • In Vitro Techniques
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Nanoparticles*
  • Percutaneous Coronary Intervention / methods*
  • Sirolimus / administration & dosage*
  • Sirolimus / pharmacokinetics
  • Sirolimus / pharmacology

Substances

  • Chromium Alloys
  • Sirolimus