Stent-mediated methylprednisolone delivery reduces macrophage contents and in-stent neointimal formation.
OBJECTIVE
Corticosteroids have a wide range of biological effects. Stent-based methylprednisolone delivery could effectively suppress peri-strut inflammation and neointima induced by a polymer matrix. We tested the safety and efficacy of local stent-mediated methylprednisolone delivery using a biological coating on in-stent neointimal formation in a porcine coronary stent model.


METHODS
Stainless steel coronary stents were dip-coated in a biological polymer/ methylprednisolone solution, resulting in total load of 530 mug methylprednisolone per stent. In-vitro drug release was performed. Stainless steel bare stents, polymer-only and methylprednisolone-coated stents (MP) were implanted in coronary arteries of pigs with a stent/artery ratio of 1.2 : 1. Histopathologic evaluation, morphometry and immunohistochemistic staining were analyzed at 4-week follow-up.


RESULTS
In-vitro drug release studies showed sustained release up to 10 weeks. In vivo the vascular response of polymer-only-coated stents was comparable with the bare stents. No increased peri-strut inflammation and neointimal hyperplasia were observed. The in-stent neointimal formation of methylprednisolone-coated stents was significantly reduced compared with the bare and polymer-only-coated stents (bare, 1.92+/-0.73; polymer-only, 2.14+/-1.50; MP, 1.01+/-0.47 mm, P=0.019). The macrophage content of methylprednisolone-coated stents (bare, 30.74+/-48.67; polymer-only, 19.55+/-24.60; MP, 1.16+/-3.33/mm, P=0.072) was dramatically decreased. However, there were no significant difference among the three group in terms of the proliferating cells expressed by proliferation cell nuclear antigens.


CONCLUSIONS
Stent-based local methylprednisolone delivery could effectively decrease both vascular macrophage infiltration and in-stent neointimal hyperplasia.
Wang
Lan
L
Department of Cardiology and Pathology, University of Leuven, Belgium.
Salu
Koen
K
Verbeken
Eric
E
Bosmans
Johan
J
Van de Werf
Frans
F
De Scheerder
Ivan
I
Huang
Yanming
Y
D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D049109:Cell Proliferation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D006965:Hyperplasia / Q000517:prevention & control; D007150:Immunohistochemistry; D008264:Macrophages; D008297:Male; D008775:Methylprednisolone / Q000493:pharmacokinetics / Q000494:pharmacology*; D011336:Probability; D012680:Sensitivity and Specificity; D015607:Stents; D034421:Sus scrofa; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects*
D008775:Methylprednisolone