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Promoting endothelial recovery and reducing neointimal hyperplasia using sequential-like release of acetylsalicylic acid and paclitaxel-loaded biodegradable stents

Authors Lee CH, Yu CY, Chang SH, Hung KC, Liu SJ, Wang CJ, Hsu MY, Hsieh IC, Chen WJ, Ko YS, Wen MS

Received 14 May 2014

Accepted for publication 21 June 2014

Published 27 August 2014 Volume 2014:9(1) Pages 4117—4133

DOI https://doi.org/10.2147/IJN.S67721

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Supplementary video showing no migration of the implanted stent (arrows) was observed at 3 days and 4 weeks following the procedure, and the stented abdominal aorta was patent for all test animals based on the peripheral vascular ultrasound study.

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Cheng-Hung Lee,1,2 Chia-Ying Yu,2 Shang-Hung Chang,1 Kuo-Chun Hung,1 Shih-Jung Liu,2 Chao-Jan Wang,3 Ming-Yi Hsu,3 I-Chang Hsieh,1 Wei-Jan Chen,1 Yu-Shien Ko,1 Ming-Shien Wen1

1Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Tao-Yuan, Taiwan; 2Department of Mechanical Engineering, Chang Gung University, Tao-Yuan, Taiwan; 3Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital, Linkou, Tao-Yuan, Taiwan

Introduction: This work reports on the development of a biodegradable dual-drug-eluting stent with sequential-like and sustainable drug-release of anti-platelet acetylsalicylic acid and anti-smooth muscle cell (SMC) proliferative paclitaxel.
Methods: To fabricate the biodegradable stents, poly-L-lactide strips are first cut from a solvent-casted film. They are rolled onto the surface of a metal pin to form spiral stents. The stents are then consecutively covered by acetylsalicylic acid and paclitaxel-loaded polylactide-polyglycolide nanofibers via electrospinning.
Results: Biodegradable stents exhibit mechanical properties that are superior to those of metallic stents. Biodegradable stents sequentially release high concentrations of acetylsalicylic acid and paclitaxel for more than 30 and 60 days, respectively. In vitro, the eluted drugs promote endothelial cell numbers on days 3 and 7, and reduce the proliferation of SMCs in weeks 2, 4, and 8. The stents markedly inhibit the adhesion of platelets on days 3, 7, and 14 relative to a non-drug-eluting stent. In vivo, the implanted stent is intact, and no stent thrombosis is observed in the stent-implanted vessels without the administration of daily oral acetylsalicylic acid. Promotion of endothelial recovery and inhibition of neointimal hyperplasia are also observed on the stented vessels.
Conclusion: The work demonstrates the efficiency and safety of the biodegradable dual-drug-eluting stents with sequential and sustainable drug release to diseased arteries.

Keywords: sequential-like and sustainable release, biodegradable drug-eluting stents, poly-L-lactide, polylactide-polyglycolide, mechanical properties
 

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