title: Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and Atherosclerotic Arteries - First Experimental Results in Rabbits at Low Inflation Pressure.
abstract: OBJECTIVE
  Beyond antiproliferative properties, paclitaxel exhibits anti-inflammatory activity, which might be beneficial in the local treatment of nonocclusive coronary artery disease. Paclitaxel release and tissue concentrations after paclitaxel-coated balloon treatment using different pressures have not been investigated so far. The aim of the study was to investigate in an atherosclerotic rabbit model whether drug transfer from paclitaxel-coated balloons into the vessel wall is affected by the presence of atherosclerotic lesions and to which extent it depends on the inflation pressure used.
  
  
  METHODS
  Paclitaxel-coated balloons (3.5 μg/mm(2) paclitaxel) were inflated with pressures of 1, 2, or 6 atm (60s) in healthy (n = 39) and atherosclerotic (n = 22) arteries of New Zealand White Rabbits. Paclitaxel content in arterial walls (10 min after interventions) and paclitaxel remaining on balloons after treatment were analyzed using high-performance liquid chromatography.
  
  
  RESULTS
  Median paclitaxel tissue concentrations were 829.3 μg/g (IQR 636.5-1487 μg/g) in healthy and 375.7 μg/g (IQR 169.8-771.6 μg/g) in atherosclerotic arteries (p = 0.0002). The paclitaxel tissue concentration was dependent on inflation pressure (1 atm vs. 2 atm vs. 6 atm) in atherosclerotic arteries (p = 0.0106) but not in healthy arteries (p ≥ 0.05).
  
  
  CONCLUSIONS
  Atherosclerotic lesions impede the transfer of paclitaxel into arterial walls. Higher inflation pressures resulted in an increased paclitaxel transfer in atherosclerotic but not in healthy arteries. However, it is assumed that the tissue concentrations achieved with an inflation pressure of 2 atm are potentially effective in this model.
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany. nicola.stolzenburg@charite.de.
authors.forename: Nicola
authors.initials: N
authors.lastname: Stolzenburg
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Janni
authors.initials: J
authors.lastname: Breinl
authors.affiliation: InnoRa GmbH, Berlin, Germany.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Bienek
authors.affiliation: Department of Cardiology, Charité - Universitätsmedizin Berlin, Campus Benjamin Franklin, Berlin, Germany.
authors.forename: Milosz
authors.initials: M
authors.lastname: Jaguszewski
authors.affiliation: InnoRa GmbH, Berlin, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Löchel
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Taupitz
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany.|InnoRa GmbH, Berlin, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Speck
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Wagner
authors.affiliation: Department of Radiology, Section of Experimental Radiology, Charité - Universitätsmedizin Berlin, Campus Charité Mitte, Charitéplatz 1, 10117, Berlin, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Schnorr
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000493:pharmacokinetics; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems; D008297:Male; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011817:Rabbits
chemical_list: D000893:Anti-Inflammatory Agents; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel
keywords: Atherosclerotic plaque; Atherosclerotic rabbit model; Drug-coated balloon; Inflation pressure; Paclitaxel