title: 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.
abstract: OBJECTIVE
  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.
  
  
  BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Skirball Center for Cardiovascular Research for Cardiovascular Research Foundation, Orangeburg, New York 10962, USA.
authors: Piotr P
authors: PP
authors: Buszman
authors: Armando
authors: A
authors: Tellez
authors: Maxwell E
authors: ME
authors: Afari
authors: Athanasios
authors: A
authors: Peppas
authors: Gerard B
authors: GB
authors: Conditt
authors: Serge D
authors: SD
authors: Rousselle
authors: Jennifer C
authors: JC
authors: McGregor
authors: Mark
authors: M
authors: Stenoien
authors: Greg L
authors: GL
authors: Kaluza
authors: Juan F
authors: JF
authors: Granada
mesh_terms: D000800:Angioplasty, Balloon / Q000009:adverse effects / Q000295:instrumentation*; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000209:etiology; D002317:Cardiovascular Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D049109:Cell Proliferation / Q000187:drug effects; D020099:Coated Materials, Biocompatible; D003251:Constriction, Pathologic; D003287:Contrast Media; D004195:Disease Models, Animal; D004867:Equipment Design; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005355:Fibrosis; D006938:Hyperlipoproteinemia Type II / Q000150:complications; D007083:Iliac Artery / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007472:Iohexol / Q000031:analogs & derivatives*; D058426:Neointima; D017239:Paclitaxel / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011859:Radiography; D034421:Sus scrofa; D014018:Tissue Distribution; D062666:Vascular Access Devices; D014945:Wound Healing / Q000187:drug effects*
chemical_list: D002317:Cardiovascular Agents; D020099:Coated Materials, Biocompatible; D003287:Contrast Media; D007472:Iohexol; C038192:iopromide; D017239:Paclitaxel
keywords: %AS; %DS; EEL; FHS; IEL; ISR; MLD; PBA; PCB; QVA; RVD; external elastic lamina; familial hypercholesterolemic swine; in-stent restenosis; in-stent restenosis model; internal elastic lamina; minimal lumen diameter; paclitaxel-coated balloon; percentage of area stenosis; percentage of diameter stenosis; plain balloon angioplasty; quantitative vascular angiography; reference vessel diameter; second-generation