Attainment of local drug delivery with paclitaxel-eluting balloon in porcine coronary arteries.
ABSTRACT Our purpose was to confirm the local drug delivery of a paclitaxel-eluting balloon by percutaneous intervention of single arterial segments or bifurcations of porcine coronary arteries.
Eight domestic pigs were subjected to 2 x 30 s Dior balloon dilatation of the mid left anterior descending, left circumflex and proximal right coronary arteries. Bifurcation intervention was performed in six arteries. The dilated, and the distal and proximal reference segments were prepared for tissue paclitaxel concentration measurement. Tissue samples were harvested at mean 1.5, 12, 24 and 48 h after balloon dilatation and plasma samples were taken at various time points.
The tissue paclitaxel concentration of the single dilated segment was at 1.5 h postdilatation 1.82+/-1.60 micromol/l, which decreased significantly to 0.73+/-0.27 (P=0.032), 0.62+/-0.34 and 0.44+/-0.31 micromol/l at 12, 24 and 48 h. The bifurcation intervention resulted in 5.10+/-1.80 micromol/l tissue paclitaxel amount in the main branch, which at 12 h had diminished to 1.41+/-1.23 micromol/l (P=0.004). The bifurcation side contained 7.00+/-4.80 micromol/l paclitaxel at 1.5 h postdilatation, which lowered to 2.72+/-0.40 micromol/l (P=0.034). The mean paclitaxel concentration of the reference segments decreased gradually from 0.84+/-0.99 to 0.34+/-0.36 micromol/l (P=0.09), 0.28+/-0.16 and 0.19+/-0.18 micromol/l tissue at 1.5, 12, 24 and 48 h postdilatation, respectively. No paclitaxel was found in the peripheral blood at any time point.
Short exposure of the coronary artery to paclitaxel with a coated balloon is sufficient for the attainment of an adequate tissue concentration of paclitaxel, which is known to be efficient in inhibiting neointimal growth.
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ABSTRACT: Background Despite advancements from balloon angioplasty to drug-eluting stents, primary patency rates after endovascular revascularization of peripheral artery disease have remained inferior compared to surgery. Endovascular revascularization has been limited by restenosis and mechanical stent failure. Thus, there is increased research into other nonstent-based local drug delivery modalities, which can provide an active drug to inhibit restenosis focally and avoid the risk of systemic adverse effects.Methods This review will summarize the unique properties of paclitaxel and studies on paclitaxel local delivery for the treatment of peripheral artery disease. A MEDLINE search for relevant peer-reviewed scientific literature published in English was conducted. Search terms included but were not limited to paclitaxel pharmacodynamics, paclitaxel local drug delivery, and drug eluting balloons, with a focus on the use of paclitaxel in the context of coronary and peripheral vascular disease.ResultsThe primary search produced 182 results of which 51 papers were relevant. Of the 51 relevant papers, 27 were original research papers and 24 were either review papers, commentary or opinion papers.Conclusions Paclitaxel has several chemical properties, which make it ideal for local drug delivery including its hydrophobicity, ability to concentrate into the arterial intima layer and prolonged effect on cells even after brief exposure periods. Local delivery of paclitaxel via injection catheters, balloon catheters and coated balloons has shown encouraging results in terms of efficacy and safety in small-scale animal and clinical studies. Additional preclinical and clinical studies are needed to determine the long-term efficacy and safety of these treatments in humans.European Journal of Clinical Investigation 01/2015; 45(3). DOI:10.1111/eci.12407 · 2.83 Impact Factor
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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.07/2014; 1(1):e000117. DOI:10.1136/openhrt-2014-000117