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.
- SourceAvailable from: Piotr P Buszman[Show abstract] [Hide abstract]
ABSTRACT: Background: New paclitaxel coated balloons (PCB) developments have been proposed to maintain therapeutic levels of drug in the tissue while decreasing particle release. In this series of studies, we evaluated the pharmacokinetic profile and biological effects after paclitaxel delivery via novel microcrystalline PCB coating (mcPCB, Pax®, Balton) in porcine iliofemoral arteries. Methods: Ten domestic swine were enrolled yielding 24 iliofemoral segments for evaluation. In the pharmacokinetic study, nine mcPCBs were dilated for 60 sec and animals sacrificed after 1 hr, 3 and 7 days. Studied segments were harvested and tissue paclitaxel concentration was analyzed utilizing HPLC. In the biological response evaluation, self-expandable stents were implanted followed by post dilation with either mcPCB (n = 10) or POBA (n = 5). After 28 days, angiography was performed, animals were sacrificed and stented segments harvested for histopathological evaluation. Results: The 1-hr, 3 and 7 days vessel paclitaxel concentrations were 152.9 ± 154.5, 36.5 ± 49.5, and 0.9 ± 0.7 ng/mg respectively. In the biological response study, stents in the mcPCB group presented lower angiographic measures of neointimal hyperplasia as expressed by late loss when compared to POBA (-0.43 ± 0.9 vs. 0.23 ± 1.2; P = 0.24) at 28 days. In the histopathological evaluation, percent area of stenosis (%AS) was reduced by 42% in the mcPCB group (P < 0.05). The healing process in mcPCB group was comparable to POBA with regard to fibrin deposition (0.7 vs. 0.7; P = ns), neointimal maturity (1.97 vs. 1.93; P = ns), inflammation score (0.92 vs. 1; P = ns) and endothelialization score (1.77 vs. 1.73; P = ns). The mcPCB group did however display a greater tendency of medial cell loss and mineralization (60% vs. 0; P = 0.08). Conclusions: Delivery of paclitaxel via a novel mcPCB resulted in low long-term tissue retention of paclitaxel. However, this technological approach displayed reduced neointimal proliferation and favorable healing profile. © 2013 Wiley Periodicals, Inc.Catheterization and Cardiovascular Interventions 05/2013; · 2.51 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Over the last few years, drug-coated balloon (DCB) therapy has emerged as a promising therapeutic intervention for the management of obstructive cardiovascular disease. The dictum of this novel technology is that effective prevention of restenosis can be achieved by the short-term transfer of antiproliferative drug to local arterial tissue by means of a single prolonged balloon angioplasty dilatation. Its main attraction is that no foreign body is implanted eliminating thus the risk of late inflammatory response to device components without preventing positive remodeling. Here, we discuss the evidence regarding the effectiveness of DCB in different lesion types and clinical settings as well as the types of DCB commercially available or under development.Expert Review of Cardiovascular Therapy 10/2013; 11(10):1379-91.
- [Show abstract] [Hide abstract]
ABSTRACT: This study sought to evaluate vascular drug uptake, distribution and response of second-generation paclitaxel coated balloon (PCB) (Cotavance, MEDRAD Interventional, Indianola, Pennsylvania) and compare it with first-generation technology, containing identical excipient and drug concentration. Original PCB technologies displayed a heterogeneous deposition of crystalline paclitaxel-iopromide inside the balloon folds, whereas second-generation PCBs consisted of more homogeneous, circumferential coatings. Paclitaxel tissue uptake was assessed in 20 iliofemoral arteries of a domestic swine. Vascular healing response was assessed in the familial hypercholesterolemic model of iliofemoral in-stent restenosis. Three weeks after bare-metal stent implantation, vascular segments were randomly revascularized with first-generation PCBs (n = 6), second-generation PCBs (n = 6), or plain balloon angioplasty (PBA) (n = 6). At 28 days, angiographic and histological evaluation was performed in all treated segments. One-hour paclitaxel tissue uptake was 42% higher in the second-generation PCBs (p = 0.03) and resulted in more homogeneous segment-to-segment distribution compared with first-generation PCBs. Both angiography (percentage of diameter stenosis: second-generation 11.5 ± 11% vs. first-generation 21.9 ± 11% vs. PBA 46.5 ± 10%; p < 0.01) and histology (percentage of area stenosis: second-generation 50.5 ± 7% vs. first-generation 54.8 ± 18% vs. PBA 78.2 ± 9%; p < 0.01) showed a decrease in neointimal proliferation in both PCB groups. Histological variance of the percentage of area stenosis was lower in second-generation compared with first-generation PCBs (51.7 vs. 328.3; p = 0.05). The presence of peristrut fibrin deposits (0.5 vs. 2.4; p < 0.01) and medial smooth muscle cell loss (0 vs. 1.7; p < 0.01) were lower in the second-generation compared with first-generation PCBs. In the experimental setting, second-generation PCB showed a comparable efficacy profile and more favorable vascular healing response when compared to first-generation PCB. The clinical implications of these findings require further investigation.JACC Cardiovascular Interventions 08/2013; 6(8):883-90. · 7.42 Impact Factor