The behavior of vascular smooth muscle cells and platelets onto epigallocatechin gallate-releasing poly(l-lactide-co-ε-caprolactone) as stent-coating materials

摘要

Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, thrombosis, inflammation, and restenosis are still major problems for the utility of cardiovascular prostheses such as vascular grafts and stents. Epigallocatechin-3-O-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to have anti-thrombotic, anti-inflammatory and anti-proliferative activities. It was hypothesized that controlled release of EGCG from biodegradable poly(lactide-co-ε-caprolactone, PLCL) stent coatings would suppress migration and invasion of vascular smooth muscle cells (VSMCs) as well as platelet-mediated thrombosis. EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with 5% EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG did, however, EGCG appreciably increase the hydrophilicity of PLCL. EGCG was found to be uniformly dispersed throughout E-PLCL without direct chemical interactions with PLCL. E-PLCL displayed diffusion controlled release of EGCG release for periods up to 34 days. E-PLCL significantly suppressed the migration and invasion of VSMCs as well as the adhesion and activation of platelets. E-PLCL coatings were able to smooth the surface of bare stents with neither cracks nor webbings after balloon expansion. The structural integrity of coatings was sufficient to resist delamination or destruction during 90% dilatation. These results suggest that EGCG-releasing polymers can be effectively applied for fabricating an EGCG-eluting vascular stent to prevent in-stent restenosis and thrombosis.