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Stent-mediated methylprednisolone delivery reduces macrophage contents and in-stent neointimal formation

Wang, Lana b; Salu, Koend; Verbeken, Erica; Bosmans, Johand; Van de Werf, Fransa; De Scheerder, Ivana; Huang, Yanminga c

Therapy and Prevention
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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 μg 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 mm2, 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/mm2, 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.

Stent-based methylprednisolone delivery could suppress peristrut inflammation and neointima induced by a polymer matrix. In this study a biological coating was used for stent-based local methylprednisolone delivery. A good biocompatibility of the biological coating to arterial wall was observed. Local released methylprednisolone could effectively decrease the vascular macrophage infiltration and in-stent neointimal hyperplasia in a porcine coronary stent model.

aDepartment of Cardiology and Pathology, University of Leuven, Belgium

bDepartment of Dermatology, Tongji Hospital

cDepartment of Chinese Medicine, Xiehe Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China

dDepartment of Cardiology, University of Antwerp, Antwerp, Belgium

Correspondence and requests for reprints to Yanming Huang, MD, PhD, Department of Cardiology, U.Z Gasthuisberg O/N, University of Leuven, Herestraat 49, 3000 Leuven, Belgium

Tel: 0032 16 345935; fax: 0032 16 345844

e-mail: yanming.huang@med.kuleuven.ac.be and ming412@yahoo.com

Received 15 December 2004 Revised 17 February 2005 Accepted 25 February 2005

© 2005 Lippincott Williams & Wilkins, Inc.