Author:

Keywords:

Analysis of Variance, Animals, Biopsy, Needle, Cell Proliferation, Coronary Vessels, Disease Models, Animal, Drug Delivery Systems, Female, Hydrogen-Ion Concentration, Hyperplasia, Immunohistochemistry, Macrophages, Male, Methylprednisolone, Probability, Sensitivity and Specificity, Stents, Sus scrofa, Tunica Intima, Science & Technology, Life Sciences & Biomedicine, Cardiac & Cardiovascular Systems, Cardiovascular System & Cardiology, methylprednisolone, stent, restenosis, DEXAMETHASONE-ELUTING STENT, PORCINE CORONARY-ARTERIES, LOCAL-DELIVERY, INTIMAL HYPERPLASIA, BALLOON ANGIOPLASTY, RESTENOSIS, IMPLANTATION, INJURY, HUMANS, MODEL, 1103 Clinical Sciences, Cardiovascular System & Hematology, 3201 Cardiovascular medicine and haematology, 3202 Clinical sciences

Abstract:

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. CONCLUSION: Stent-based local methylprednisolone delivery could effectively decrease both vascular macrophage infiltration and in-stent neointimal hyperplasia.