Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and Atherosclerotic Arteries - First Experimental Results in Rabbits at Low Inflation Pressure.

Nicola Stolzenburg,Stephanie Bienek,Susanne Wagner,Matthias Taupitz,Ulrich Speck,Melanie Löchel,Janni Breinl,Jörg Schnorr,Milosz Jaguszewski

doi:10.1007/s10557-016-6658-1

Paclitaxel-Coated Balloons: Investigation of Drug Transfer in Healthy and Atherosclerotic Arteries - First Experimental Results in Rabbits at Low Inflation Pressure.

Nicola Stolzenburg, Stephanie Bienek + Show 7 more

Open Access

https://doi.org/10.1007/s10557-016-6658-1

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Abstract

PurposeBeyond 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.MethodsPaclitaxel-coated balloons (3.5 μg/mm2 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.ResultsMedian 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).ConclusionsAtherosclerotic 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.

Highlights

The use of drug-eluting stents (DES) has significantly reduced the reintervention rate for repeat target lesion revascularization in coronary arteries due to restenosis to below 10 % [1,2,3,4]
Atherosclerotic lesions impede the transfer of paclitaxel into arterial walls
It is assumed that the tissue concentrations achieved with an inflation pressure of 2 atm are potentially effective in this model

Summary

Introduction

The use of drug-eluting stents (DES) has significantly reduced the reintervention rate for repeat target lesion revascularization in coronary arteries due to restenosis to below 10 % [1,2,3,4]. Since 2009, paclitaxel-coated balloons (PCB) have been successfully used for different indications including local treatment of coronary in-stent restenosis and of stenosis and restenosis in the peripheral arteries [5,6,7,8,9]. In patients with unstable atherosclerotic lesions, delivery of a high enough concentration of paclitaxel from the PCB should be ensured at low inflation pressure. Biological factors such as local inflammatory reactions or intraplaque hemorrhage and mechanical factors may result in weakening and rupture of vulnerable or unstable plaques [16, 17]

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