Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model.
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.
Scheller
Bruno
B
Internal Medicine III, University of Saarland, D-66421 Homburg/Saar, Germany. bruno.scheller@uniklinik-saarland.de
Speck
Ulrich
U
Romeike
Bernd
B
Schmitt
Alexander
A
Sovak
Milos
M
Böhm
Michael
M
Stoll
Hans Peter
HP
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
D003287:Contrast Media; D004337:Drug Carriers; D043823:Taxoids; D007472:Iohexol; C038192:iopromide; C434865:protaxel; D017239:Paclitaxel