title: Succinobucol-eluting stents increase neointimal thickening and peri-strut inflammation in a porcine coronary model.
abstract: OBJECTIVE
  The aim of this study was to assess the efficacy of stent-based delivery of succinobucol alone and in combination with rapamycin in a porcine coronary model.
  
  
  BACKGROUND
  Current drugs and polymers used to coat coronary stents remain suboptimal in terms of long term efficacy and safety. Succinobucol is a novel derivative of probucol with improved antioxidant and anti-inflammatory properties.
  
  
  METHODS
  Polymer-free Yukon stents were coated with 1% succinobucol (SucES), 2% rapamycin (RES), or 1% succinobucol plus 2% rapamycin solutions (SucRES) and compared with a bare metal stent (BMS).
  
  
  RESULTS
  The in vivo release profile of SucES indicated drug release up to 28 days (60% drug released at 7 days); 41 stents (BMS, n = 11; SucES, n =10; RES, n = 10; SucRES, n = 10) were implanted in the coronary arteries of 17 pigs. After 28 days, mean neointimal thickness was 0.31 ± 0.14 mm for BMS, 0.51 ± 0.14 mm for SucES, 0.19 ± 0.11 mm for RES, and 0.36 ± 0.17 mm for SucRES (P < 0.05 for SucES vs. BMS). SucES increased inflammation and fibrin deposition compared with BMS (P < 0.05), whereas RES reduced inflammation compared with BMS (P < 0.05).
  
  
  CONCLUSIONS
  In this model, stent-based delivery of 1% succinobucol using a polymer-free stent platform increased neointimal formation and inflammation following coronary stenting.
authors.affiliation: Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, United Kingdom. jonnywatt@hotmail.com
authors.forename: Jonathan
authors.initials: J
authors.lastname: Watt
authors.forename: Simon
authors.initials: S
authors.lastname: Kennedy
authors.forename: Christopher
authors.initials: C
authors.lastname: McCormick
authors.forename: Ejaife O
authors.initials: EO
authors.lastname: Agbani
authors.forename: Allan
authors.initials: A
authors.lastname: McPhaden
authors.forename: Alexander
authors.initials: A
authors.lastname: Mullen
authors.forename: Peter
authors.initials: P
authors.lastname: Czudaj
authors.forename: Boris
authors.initials: B
authors.lastname: Behnisch
authors.forename: Roger M
authors.initials: RM
authors.lastname: Wadsworth
authors.forename: Keith G
authors.initials: KG
authors.lastname: Oldroyd
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity*; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000187:drug effects / Q000473:pathology; D005337:Fibrin / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008297:Male; D008670:Metals; D023421:Models, Animal; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000473:pathology; D058426:Neointima; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects / Q000295:instrumentation*; D011341:Probucol / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D011474:Prosthesis Design; D020123:Sirolimus / Q000008:administration & dosage; D013552:Swine
chemical_list: D002317:Cardiovascular Agents; D008670:Metals; D005337:Fibrin; C471047:succinobucol; D011341:Probucol; D020123:Sirolimus