title: Pathological analysis of local delivery of paclitaxel via a polymer-coated stent.
abstract: BACKGROUND
  Paclitaxel can inhibit vascular smooth muscle proliferation in vitro, and early studies suggest that paclitaxel may be useful in preventing restenosis. Early and late intimal growth and local vascular pathological changes associated with paclitaxel delivered via stents have not been fully explored.
  
  
  RESULTS
  Localized drug delivery was accomplished with balloon-expandable stainless steel stents coated with a cross-linked biodegradable polymer, chondroitin sulfate and gelatin (CSG), containing various doses of paclitaxel. CSG-coated stents with paclitaxel (42.0, 20.2, 8.6, or 1.5 microgram of paclitaxel per stent), CSG-coated stents without paclitaxel, and uncoated stents (without paclitaxel or CSG) were deployed in the iliac arteries of New Zealand White rabbits, which were killed 28 days after implant. Mean neointimal thickness at stent strut sites was reduced 49% (P<0.0003) and 36% (P<0.007) with stents containing 42.0 and 20.2 microgram of paclitaxel per stent, respectively, versus CSG-coated stents without paclitaxel. However, histological findings suggested incomplete healing in the higher-dose (42.0 and 20.2 microgram) paclitaxel-containing stents consisting of persistent intimal fibrin deposition, intraintimal hemorrhage, and increased intimal and adventitial inflammation. Stents coated with CSG alone (without paclitaxel) had similar neointimal growth as uncoated stents. In a separate group of rabbits killed at 90 days, neointimal growth was no longer suppressed by CSG-coated stents containing 42.0 or 21.0 microgram of paclitaxel
  
  
  CONCLUSIONS
  CSG coating appears to be a promising medium for localized drug delivery. Paclitaxel polymer-coated stents reduce neointima formation but are associated with evidence of incomplete healing at 28 days. However, neointimal suppression was not maintained at 90 days.
authors.affiliation: Department of Cardiovascular Pathology, Armed Forces Institute of Pathology, Washington, DC, USA.
authors.forename: A
authors.initials: A
authors.lastname: Farb
authors.forename: P F
authors.initials: PF
authors.lastname: Heller
authors.forename: S
authors.initials: S
authors.lastname: Shroff
authors.forename: L
authors.initials: L
authors.lastname: Cheng
authors.forename: F D
authors.initials: FD
authors.lastname: Kolodgie
authors.forename: A J
authors.initials: AJ
authors.lastname: Carter
authors.forename: D S
authors.initials: DS
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: Froehlich
authors.forename: R
authors.initials: R
authors.lastname: Virmani
mesh_terms: D020533:Angiogenesis Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002809:Chondroitin Sulfates; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems / Q000379:methods*; D005337:Fibrin / Q000187:drug effects / Q000378:metabolism; D005780:Gelatin; D006470:Hemorrhage / Q000139:chemically induced / Q000473:pathology; D007083:Iliac Artery / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology; D008297:Male; D017239:Paclitaxel / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011108:Polymers; D011817:Rabbits; D015607:Stents; D013997:Time Factors; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D011108:Polymers; D005780:Gelatin; D005337:Fibrin; D002809:Chondroitin Sulfates; D017239:Paclitaxel