A novel polymer-free paclitaxel-eluting stent with a nanoporous surface for rapid endothelialization and inhibition of intimal hyperplasia: Comparison with a polymer-based sirolimus-eluting stent and bare metal stent in a porcine model

J Biomed Mater Res A. 2011 Sep 15;98(4):629-37. doi: 10.1002/jbm.a.33151. Epub 2011 Jul 5.

Abstract

Hypersensitivity and inflammatory responses to polymers may be responsible for late stent thrombosis after implantation of a drug-eluting stent (DES). Polymer-free DES may reduce the prevalence of these adverse reactions in vessels. We evaluated a polymer-free paclitaxel-eluting-stent with a nanoporous surface (nano-PES) for endothelialization and inhibition of neointimal hyperplasia by optical coherence tomography (OCT) and pathology in a porcine model. Nano-PES with high-dose (HD) and low-dose (LD) paclitaxel (1.0 μg/mm(2) and 0.4 μg/mm(2), respectively) was compared with a sirolimus-eluting stent (SES) and bare-metal stent (BMS) in a porcine model. Fifty-three stents (14 HD, 14 LD, 14 SES, 11 BMS) were implanted in 18 minipigs. At 14 days, nano-PES with HD and LD showed more complete endothelialization compared with SES. BMS had 100% endothelial coverage. At 28 days, a significant reduction in neointimal hyperplasia was detected by OCT in the nano-PES HD group compared with BMS. No benefit in prevention of the neointimal hyperplasia was observed in the nano-PES LD group. Nano-PES stents showed decreased deposition of fibrin and inflammation compared with SES. Pharmacokinetic studies revealed that nano-PES could effectively deliver the drug to the local coronary artery and it released the drug more rapidly than SES. Such a release profile was favorable for rapid endothelialization of nano-PES. The present study showed the nano-PES to be a new drug-delivery technology; that it used a nanoporous stent surface; that it offered desirable drug-elution properties without the use of polymers; that it may translate into an improved safety profile for next-generation DES.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Coronary Angiography
  • Drug Carriers / chemistry
  • Drug-Eluting Stents*
  • Hyperplasia / drug therapy*
  • Hyperplasia / pathology
  • Materials Testing
  • Metals / chemistry
  • Nanostructures / chemistry
  • Paclitaxel / pharmacokinetics
  • Paclitaxel / pharmacology*
  • Paclitaxel / therapeutic use*
  • Polymers / chemistry
  • Porosity
  • Stents
  • Surface Properties
  • Swine
  • Swine, Miniature
  • Tomography, Optical Coherence
  • Tunica Intima / drug effects*
  • Tunica Intima / pathology

Substances

  • Antineoplastic Agents, Phytogenic
  • Drug Carriers
  • Metals
  • Polymers
  • Paclitaxel