Tissue uptake, distribution, and healing response after delivery of paclitaxel via second-generation iopromide-based balloon coating: a comparison with the first-generation technology in the iliofemoral porcine model

• Published in: JACC. Cardiovascular interventions 2013-08, Vol.6 (8), p.883-890
• Main Authors: Buszman, Piotr P, Tellez, Armando, Afari, Maxwell E, Peppas, Athanasios, Conditt, Gerard B, Rousselle, Serge D, McGregor, Jennifer C, Stenoien, Mark, Kaluza, Greg L, Granada, Juan F
• Format: Article
• Language: English
• Subjects: Angioplasty, Balloon - adverse effects; Angioplasty, Balloon - instrumentation; Animals; Arterial Occlusive Diseases - diagnosis; Arterial Occlusive Diseases - drug therapy; Arterial Occlusive Diseases - etiology; Cardiovascular Agents - administration & dosage; Cardiovascular Agents - pharmacokinetics; Cell Proliferation - drug effects; Coated Materials, Biocompatible; Constriction, Pathologic; Contrast Media; Disease Models, Animal; Equipment Design; Femoral Artery - diagnostic imaging; Femoral Artery - drug effects; Femoral Artery - metabolism; Femoral Artery - pathology; Fibrosis; Hyperlipoproteinemia Type II - complications; Iliac Artery - diagnostic imaging; Iliac Artery - drug effects; Iliac Artery - metabolism; Iliac Artery - pathology; Iohexol - analogs & derivatives; Neointima; Paclitaxel - administration & dosage; Paclitaxel - pharmacokinetics; Radiography; Sus scrofa; Tissue Distribution; Vascular Access Devices; Wound Healing - drug effects
• ISSN: 1876-7605
• DOI: 10.1016/j.jcin.2013.04.013

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.