title: Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.
abstract: BACKGROUND
  Lipophilic taxanes can be dissolved in contrast media at significantly higher concentration than in saline. As contrast media have occasionally been observed to delineate the contour of coronary arteries for some seconds they may serve as a matrix for an antiproliferative drug aimed at preventing restenosis. The aim of this study was to test a novel taxane-contrast agent formulation for this new approach in the setting of coronary stenting.
  
  
  RESULTS
  In cell culture experiments (bovine vascular smooth muscle cells), 60-min incubation with contrast agent-taxane formulations (iopromide-paclitaxel, iopromide-protaxel) induced a significant, concentration-dependent inhibition of vascular smooth muscle cell (VSMC) proliferation over 12 days. Shorter incubation times of 10 and 3 min showed the same efficacy. For in vivo investigation, 16 stents were implanted into the coronary arteries of eight pigs using a 1.3 to 1 overstretch ratio. A control group received iopromide 370 alone while the treatment group was injected with a iopromide-protaxel formulation at a dose of 74 micromol/l, which is far below protaxel levels inducing systemic toxicity. Quantitative angiography and histomorphometry of the stented arteries asserted statistic equality of the baseline parameters between the control and treatment groups. After 28 days, the treatment group showed a marked reduction of the parameters characterizing in-stent restenosis, especially a 34% reduction of the neointimal area.
  
  
  CONCLUSIONS
  First evidence is provided that using a contrast agent as solvent for a taxane constitutes a new drug delivery mechanism able to inhibit in-stent restenosis in the porcine restenosis model.
authors.affiliation: Internal Medicine III, University of Saarland, D-66421 Homburg/Saar, Germany. bruno.scheller@uniklinik-saarland.de
authors.forename: Bruno
authors.initials: B
authors.lastname: Scheller
authors.forename: Ulrich
authors.initials: U
authors.lastname: Speck
authors.forename: Bernd
authors.initials: B
authors.lastname: Romeike
authors.forename: Alexander
authors.initials: A
authors.lastname: Schmitt
authors.forename: Milos
authors.initials: M
authors.lastname: Sovak
authors.forename: Michael
authors.initials: M
authors.lastname: Böhm
authors.forename: Hans Peter
authors.initials: HP
authors.lastname: Stoll
mesh_terms: D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003287:Contrast Media / Q000008:administration & dosage*; D023903:Coronary Restenosis / Q000473:pathology / Q000517:prevention & control; D004337:Drug Carriers; D005240:Feasibility Studies; D007472:Iohexol / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D017239:Paclitaxel / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D015607:Stents; D013552:Swine; D043823:Taxoids; D017539:Tunica Intima / Q000473:pathology
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D043823:Taxoids; D007472:Iohexol; C038192:iopromide; C434865:protaxel; D017239:Paclitaxel