Addition of cytochalasin D to a biocompatible oil stent coating inhibits intimal hyperplasia in a porcine coronary model.
BACKGROUND
Polymer-based, drug-eluting stents, are currently under extensive investigation in the conquest against in-stent restenosis. Concern remains, however, about potential long-term lack of biocompatibility of the polymers used in these studies. Therefore, this study aimed to evaluate in porcine coronary arteries (1) the in vivo biocompatibility of a new natural, eicosapentaenoic acid oil stent-coating and (2) the efficacy of this coating in preventing in-stent restenosis when cytochalasin D--an inhibitor of actin filament formation, that interferes with cell proliferation and migration--was added.


RESULTS
To assess in vivo biocompatibility of the oil coating, 15 bare and 15 oil-coated stents were randomly deployed in coronary arteries of 15 pigs. No difference in tissue response, regarding inflammation or proliferation, was seen between both groups at five days or at four weeks follow-up. To evaluate the efficacy of the coating in preventing in-stent restenosis by adding a potential anti-restenotic drug, stents were dip-coated in 20 mg cytochalasin D/ml oil solution, resulting in 93 +/- 18 microg cytochalasin D/stent load (n = 3). In vitro drug release studies showed sustained release up to four weeks. Next, 11 oil-coated and 11 cytochalasin D-loaded stents were randomly implanted in coronary arteries of 11 pigs. At four weeks, a 39% decrease in neointimal hyperplasia (p < 0.05, ANCOVA, with injury as covariate) was found in cytochalasin D-loaded stents compared to oil-coated stents.


CONCLUSIONS
This new natural oil stent-coating shows excellent biocompatibility to vascular tissue. Local cytochalasin D delivery from this stent-platform significantly inhibits neointimal hyperplasia in a porcine coronary model.
Salu
Koen J
KJ
Division of Cardiology, University of Antwerp, Wilrijk, Belgium. koen.salu@ua.ac.be
Huang
Yanming
Y
Bosmans
Johan M
JM
Liu
Xiaoshun
X
Li
Shengqiao
S
Wang
Lan
L
Verbeken
Eric
E
Bult
Hidde
H
Vrints
Chris J
CJ
De Scheerder
Ivan K
IK
D000818:Animals; D019917:Blood Vessel Prosthesis Implantation; D020099:Coated Materials, Biocompatible / Q000494:pharmacology*; D023903:Coronary Restenosis / Q000517:prevention & control; D003331:Coronary Vessels / Q000473:pathology* / Q000601:surgery*; D015638:Cytochalasin D / Q000494:pharmacology*; D004195:Disease Models, Animal; D005500:Follow-Up Studies; D006965:Hyperplasia / Q000517:prevention & control; D008422:Materials Testing; D008854:Microscopy, Electron; D008955:Models, Cardiovascular; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology*; D009821:Oils / Q000494:pharmacology*; D015607:Stents; D013552:Swine; D013997:Time Factors; D017539:Tunica Intima / Q000473:pathology / Q000601:surgery
D020099:Coated Materials, Biocompatible; D019384:Nucleic Acid Synthesis Inhibitors; D009821:Oils; D015638:Cytochalasin D