title: Mechanisms of tissue uptake and retention of paclitaxel-coated balloons: impact on neointimal proliferation and healing.
abstract: 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.
  
  
  
  The pharmacokinetic profile and differences in drug concentration (vessel surface vs arterial wall) of two different paclitaxel coating formulations (3 µg/mm(2)) 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.
  
  
  
  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.
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation , Orangeburg, New York , USA.
authors.forename: Juan F
authors.initials: JF
authors.lastname: Granada
authors.affiliation: MEDRAD Interventional , Indianola, Pennsylvania , USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Stenoien
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation , Orangeburg, New York , USA.
authors.forename: Piotr P
authors.initials: PP
authors.lastname: Buszman
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation , Orangeburg, New York , USA.
authors.forename: Armando
authors.initials: A
authors.lastname: Tellez
authors.affiliation: MEDRAD Interventional , Indianola, Pennsylvania , USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Langanki
authors.affiliation: Skirball Center for Cardiovascular Research, Cardiovascular Research Foundation , Orangeburg, New York , USA.
authors.forename: Greg L
authors.initials: GL
authors.lastname: Kaluza
authors.affiliation: Columbia University Medical Center, Center for Interventional Vascular Therapy, New York Presbyterian Hospital , New York, New York , USA.
authors.forename: Martin B
authors.initials: MB
authors.lastname: Leon
authors.affiliation: Columbia University Medical Center, Center for Interventional Vascular Therapy, New York Presbyterian Hospital , New York, New York , USA.
authors.forename: William
authors.initials: W
authors.lastname: Gray
authors.affiliation: Harvard Medical School, Massachusetts General Hospital , Boston, Massachusetts , USA.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Jaff
authors.affiliation: Minneapolis Heart Institute and Foundation, Abbott Northwestern Hospital , Minneapolis, Minnesota , USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Schwartz
keywords: Interventional Cardiology; Peripheral Vascular Disease