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

Biomaterials

PubMedID: 23199742

Yang J, Zeng Y, Zhang C, Chen YX, Yang Z, Li Y, Leng X, Kong D, Wei XQ, Sun HF, Song CX. The prevention of restenosis in vivo with a VEGF gene and paclitaxel co-eluting stent. Biomaterials. 2013;34(6):1635-43.
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.