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The prevention of restenosis in vivo with a VEGF gene and paclitaxel co-eluting stent

Yang, Jing, Zeng, Yong, Zhang, Chao, Chen, Yong-Xia, Yang, Ziying, Li, Yongjun, Leng, Xigang, Kong, Deling, Wei, Xiao-Qing, Sun, Hong-Fan and Song, Cun-Xian 2013. The prevention of restenosis in vivo with a VEGF gene and paclitaxel co-eluting stent. Biomaterials 34 (6) , pp. 1635-1643. 10.1016/j.biomaterials.2012.11.006

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Abstract

Long-term clinical studies of drug-eluting stents (DES) have reported high incidence of late thrombosis. Given the growing concern over the clinical application of this technology, we have developed a stent coated with bi-layered PLGA nanoparticles (BL-PLGA NPs) containing VEGF plasmid in the outer layer and paclitaxel (PTX) in the inner core (VEGF/PTX NPs). We hypothesized that early release of VEGF gene would promote re-endothelialization, while slow release of PTX would suppress smooth muscle cell proliferation. Using Fc plasmid as a reporter gene, we observed that Fc/PTX NPs successfully expressed Fc protein, but did not show cytotoxicity or anti-proliferative effect during the first 7 days in cell culture. In contrast, PTX NPs showed strong anti-proliferative effect staring from day 1 in culture, suggesting sequential release of gene and PTX from the BL-PLGA NPs. In vivo effects of the treated stent were assessed in mini-swines. Implantation of GFP/PTX NP-coated stents revealed efficient local GFP gene transfection at day 7. VEGF/PTX NP-coated stents showed complete re-endothelialization and significantly suppressed in-stent restenosis after 1 month compared to commercial DES. In conclusion, the VEGF/PTX NP-coated stents promote early endothelium healing while inhibit smooth muscle cell proliferation through sequential release of the VEGF gene and paclitaxel

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Subjects: Q Science > QH Natural history > QH426 Genetics
R Medicine > R Medicine (General)
Uncontrolled Keywords: Coronary stents; VEGF; Paclitaxel; Restenosis; Gene and drug delivery
Publisher: Elsevier
ISSN: 0142-9612
Last Modified: 04 Jun 2017 04:34
URI: http://orca-mwe.cf.ac.uk/id/eprint/41312

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