Copyright © 2003 by the European Society of Cardiology.
Regular Articles
Contrast media as carriers for local drug delivery
Successful inhibition of neointimal proliferation in the porcine coronary stent model
a Innere Medizin III, Universitätskliniken des Saarlandes, Homburg/Saar, Germany
b Institut für Radiologie, Charité, Berlin, Germany
c Institut für Neuropathologie, Universitätskliniken des Saarlandes, Holmbergh/Saar, Germany
d University of California, San Diego, Medical School, Department of Radiology, San Diego, USA
* Correspondence to: Dr Bruno Scheller, University of Saarland, Internal Medicine III, D 66421 Homburg/Saar, Germany. Tel: +49 6841 162 3350; fax: +49 6841 162 3350
E-mail address: bruno.scheller{at}uniklinik-saarland.de
Received 1 November 2002; revised 14 April 2003; accepted 2 June 2003
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.
Methods and 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 3min 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 74µmol/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.
Key Words: Restenosis • Stents • Angioplasty • Contrast media • Taxanes • Protaxel • Iopromide
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Werk, S. Langner, B. Reinkensmeier, H.-F. Boettcher, G. Tepe, U. Dietz, N. Hosten, B. Hamm, U. Speck, and J. Ricke Inhibition of Restenosis in Femoropopliteal Arteries: Paclitaxel-Coated Versus Uncoated Balloon: Femoral Paclitaxel Randomized Pilot Trial Circulation, September 23, 2008; 118(13): 1358 - 1365. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Tepe, T. Zeller, T. Albrecht, S. Heller, U. Schwarzwalder, J.-P. Beregi, M.D. C. D. Claussen, A. Oldenburg, B. Scheller, and U. Speck Local Delivery of Paclitaxel to Inhibit Restenosis during Angioplasty of the Leg N. Engl. J. Med., February 14, 2008; 358(7): 689 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Scheller, U. Speck, and M. Bohm Prevention of restenosis: is angioplasty the answer? Heart, May 1, 2007; 93(5): 539 - 541. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Scheller, C. Hehrlein, W. Bocksch, W. Rutsch, D. Haghi, U. Dietz, M. Bohm, and U. Speck Treatment of Coronary In-Stent Restenosis with a Paclitaxel-Coated Balloon Catheter N. Engl. J. Med., November 16, 2006; 355(20): 2113 - 2124. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Speck, B. Scheller, C. Abramjuk, C. Breitwieser, J. Dobberstein, M. Boehm, and B. Hamm Neointima Inhibition: Comparison of Effectiveness of Non-Stent-based Local Drug Delivery and a Drug-eluting Stent in Porcine Coronary Arteries. Radiology, August 1, 2006; 240(2): 411 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Scheller, U. Speck, C. Abramjuk, U. Bernhardt, M. Bohm, and G. Nickenig Paclitaxel Balloon Coating, a Novel Method for Prevention and Therapy of Restenosis Circulation, August 17, 2004; 110(7): 810 - 814. [Abstract] [Full Text] [PDF]
|
|