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Cardiovascular Research 2000 46(3):585-594; doi:10.1016/S0008-6363(00)00042-0
© 2000 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

In vitro evaluation of c7E3-Fab (ReoProTM) eluting polymer-coated coronary stents

Julia H. Barona, Anthony H. Gershlicka,*, Kai Hogrefea, Johanna Armstrongb, Cathy M. Holtb, Rajesh K. Aggarwala, Michael Azrinc, Michael Ezekowitzd and David P. de Bonoa

aDivision of Cardiology, Department of Medicine and Therapeutics, University of Leicester, Glenfield Hospital, Leicester, UK
bCardiovascular Medicine, Division of Clinical Sciences, University of Sheffield, Sheffield, UK
cDivision of Cardiology, University of Connecticut, Farmington, CT, USA
dYale University School of Medicine, New Haven, CT, USA

* Corresponding author. Tel.: +44-116-2875792; fax: +44-116-2563038

Objective: Stent thrombosis and in-stent restenosis remain problematic in certain patient sub-groups. c7E3-Fab (ReoProTM, abciximab) inhibits the platelet glycoprotein IIb/IIIa receptor as well as the smooth muscle cell {alpha}vβ3 receptor, and thus may influence both processes, especially if high local concentrations could be achieved. We have studied the adsorption and elution characteristics of c7E3-Fab on commercially available polymer-coated stents. We have also investigated the effect of such antibody binding on platelet deposition in vitro, and on antibody deposition into ex vivo human saphenous vein wall to assess whether such stents may influence stent thrombosis and restenosis. Methods and results: Adsorption was measured using a radioisotope technique after immersing segments of polymer-coated stents in c7E3-Fab solutions. Uptake was dependent on antibody concentration and duration of immersion of wire in the solution. After 22 h (at 5 mgml–1), 1146±101 ngcm–1 wire was adsorbed. In an in vitro perfusion circuit, the antibody eluted slowly, with 53% remaining after 12 days washing. To determine the value that such stents might have in clinical practise, adsorption to balloon-mounted stents was assessed at room temperature, using commercially available c7E3-Fab (2 mgml–1). Efficacy of eluting c7E3-Fab was determined by measuring deposition of 111-Indium platelets. Immersing stents in c7E3-Fab for 20 min inhibited platelet deposition by 82.3% compared to controls (P=0.018). Deployment of treated stents in ex vivo saphenous vein resulted in the deposition of c7E3-Fab in the intima and media. Conclusions: c7E3-Fab can be passively adsorbed onto polymer-coated stents. It elutes slowly and in a predictable manner, significantly inhibiting platelet deposition in vitro. These studies pave the way to developing stent-based delivery of a potent anti-platelet agent that may additionally affect smooth muscle cell activity.

KEYWORDS Stents; Platelets; Monoclonal antibodies; Restenosis; Thrombosis/embolism


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