Eptifibatide-eluting stent as an antiproliferative and antithrombotic agent: in vitro evaluation.
OBJECTIVE
Stent thrombosis and in-stent restenosis remain problematic despite drug-eluting stents (DES), especially in diabetic patients and in those with small-vessel disease. Eptifibatide inhibits the platelet glycoprotein IIb/IIIa and smooth muscle cell (SMC) avb3 receptor, thus potentially influencing both thrombosis and proliferation. The aim of the present studies was to examine the absorption and elution characteristics of eptifibatide on polymer-coated stents and investigated their effect on SMC proliferation, platelet deposition and platelet aggregation in vitro.


RESULTS
Polymer-mixed eptifibatide and H3-labeled eptifibatide were loaded onto bare metal stents. A maximum of 111 mcg of eptifibatide was loaded onto 3.0 x 18 mm stents. Drug elution characteristics were tested in a PBS perfusion circuit. Elution profile consisted of an early rapid phase (24% +/- 0.03 loss over 1 hour) followed by a sustained release with 44% +/- 2.30 still present on the stent after 30 days. Eluted eptifibatide significantly inhibited adenosine diphosphate (ADP)-induced platelet aggregation by 95% +/- 0.70 (p < 0.01). Efficacy of stents eluting eptifibatide for antiplatelet effect was determined by measuring deposition of 111indium-labeled platelets on stents. Platelet deposition was significantly reduced by 48% +/- 6 in comparison to controls (p = 0.0065). Finally, drug-loaded stents were placed in SMC culture and showed a distinct zone of cell growth inhibition within 1 mm2 (88 +/- 22 vs. 208 +/- 23 SMCs in control), and within 2 mm2 of stent (131 +/- 32 vs. 191 +/- 23 SMCs in control) (both p < 0.01).


CONCLUSIONS
Eptifibatide can be successfully loaded onto stents. It elutes in a predictable manner, significantly inhibiting platelet deposition, aggregation and SMC proliferation in vitro. These studies pave the way to developing stent-based delivery of a potent antiplatelet agent, which additionally may inhibit SMC activity.
Chitkara
Kamal
K
University of Leicester, Cardiovascular Medicine, Clinical Sciences, Glenfield Hospital, Leicester, United Kingdom. kc29@le.ac.uk
Hogrefe
Kai
K
Vasa-Nicotera
Mariuca
M
Swanson
Neil
N
Gershlick
Anthony H
AH
D015906:Angioplasty, Balloon, Coronary / Q000295:instrumentation / Q000379:methods; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D020099:Coated Materials, Biocompatible; D023903:Coronary Restenosis / Q000517:prevention & control / Q000628:therapy; D003328:Coronary Thrombosis / Q000517:prevention & control* / Q000628:therapy; D016503:Drug Delivery Systems; D000077542:Eptifibatide; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects; D010455:Peptides / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D011108:Polymers; D015607:Stents; D015912:Thrombolytic Therapy / Q000379:methods
D020099:Coated Materials, Biocompatible; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011108:Polymers; D000077542:Eptifibatide