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Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing
  1. Juan F Granada1,
  2. Mark Stenoien2,
  3. Piotr P Buszman1,
  4. Armando Tellez1,
  5. Dan Langanki2,
  6. Greg L Kaluza1,
  7. Martin B Leon3,
  8. William Gray3,
  9. Michael R Jaff4 and
  10. Robert S Schwartz5
  1. 1Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation, Orangeburg, New York, USA
  2. 2MEDRAD Interventional, Indianola, Pennsylvania, USA
  3. 3Columbia University Medical Center, Center for Interventional Vascular Therapy, New York Presbyterian Hospital, New York, New York, USA
  4. 4Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
  5. 5Minneapolis Heart Institute and Foundation, Abbott Northwestern Hospital, Minneapolis, Minnesota, USA
  1. Correspondence to Dr Juan F Granada; jgranada{at}crf.org

Abstract

Background The efficacy of paclitaxel-coated balloons (PCB) for restenosis prevention has been demonstrated in humans. However, the mechanism of action for sustained drug retention and biological efficacy following single-time drug delivery is still unknown.

Methods and results The pharmacokinetic profile and differences in drug concentration (vessel surface vs arterial wall) of two different paclitaxel coating formulations (3 µg/mm2) displaying opposite solubility characteristics (CC=crystalline vs AC=amorphous) were tested in vivo and compared with paclitaxel-eluting stents (PES). Also, the biological effect of both PCB formulations on vascular healing was tested in the porcine coronary injury model. One hour following balloon inflation, both formulations achieved similar arterial paclitaxel levels (CC=310 vs AC=245 ng/mg; p=NS). At 24 h, the CC maintained similar tissue concentrations, whereas the AC tissue levels declined by 99% (p<0.01). At this time point, arterial levels were 20-fold (CC) and 5-fold (AC) times higher compared to the PES group (p<0.05). At 28 days, arterial levels retained were 9.2% (CC) and 0.04% (AC, p<0.01) of the baseline levels. Paclitaxel concentration on the vessel surface was higher in the CC at 1 (CC=36.7% vs AC=13.1%, p<0.05) and 7 days (CC=38.4% vs AC=11%, p<0.05). In addition, the CC induced higher levels of neointimal inhibition, fibrin deposition and delayed healing compared with the AC group.

Conclusions The presence of paclitaxel deposits on the vessel surface driving diffusion into the arterial tissue in a time-dependent fashion supports the mechanism of action of PCB. This specific pharmacokinetic behaviour influences the patterns of neointimal formation and healing.

  • Interventional Cardiology
  • Peripheral Vascular Disease

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