Fluorocopolymer-coated nitinol self-expanding paclitaxel-eluting stent: pharmacokinetics and vascular biology responses in a porcine iliofemoral model

EuroIntervention. 2016 Aug 20;12(6):790-7. doi: 10.4244/EIJV12I6A128.

Abstract

Aims: Our aim was to evaluate arterial responses to paclitaxel and a novel fluorocopolymer-coated nitinol low-dose paclitaxel-eluting stent (FP-PES).

Methods and results: Human smooth muscle cell (SMC) migration was assessed after exposure to paclitaxel in vitro. For pharmacokinetics and vascular response, FP-PES or bare metal stents (BMS) were implanted in porcine iliofemoral arteries. Paclitaxel significantly inhibited human coronary and femoral artery SMC migration at doses as low as 1 pM. Inhibition was significantly greater for femoral compared with coronary artery SMCs from 1 pM to 1 μM. Pharmacokinetics showed consistent paclitaxel release from FP-PES over the study duration. The peak arterial wall paclitaxel level was 3.7 ng/mg at 10 days, with levels decreasing to 50% of peak at 60 days and 10% at 180 days. Paclitaxel was not detected in blood or remote organs. Arteriogram and histomorphometry analyses showed FP-PES significantly inhibits neointimal proliferation versus BMS at 30 and 90 days. Re-endothelialisation scores were not different between groups.

Conclusions: Paclitaxel affected femoral artery SMC migration at lower concentrations and to a greater degree than it did coronary artery SMCs. The novel FP-PES used in this preclinical study demonstrated a vascular healing response similar to BMS, while significantly inhibiting neointimal formation up to 90 days.

Publication types

  • Evaluation Study

MeSH terms

  • Alloys
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage*
  • Antineoplastic Agents, Phytogenic / pharmacokinetics
  • Cell Movement / drug effects
  • Coronary Vessels / cytology
  • Drug-Eluting Stents*
  • Femoral Artery / cytology
  • Humans
  • Models, Animal
  • Myocytes, Smooth Muscle / drug effects*
  • Neointima / prevention & control
  • Paclitaxel / administration & dosage*
  • Paclitaxel / pharmacokinetics
  • Polymers
  • Swine

Substances

  • Alloys
  • Antineoplastic Agents, Phytogenic
  • Polymers
  • nitinol
  • Paclitaxel