Dexamethasone-releasing biodegradable vascular stents - in vitro and in vivo results

摘要

Restenosis is a major complication of percutaneous transluminal angioplasty (PTA). It is characterized by contraction of vessel wall (negative remodelling) and intimal hyperplasia. Drug-releasing endovascular stents are a recent innovation used to control those complications of PTA. Sirolimus and paclitaxel have been successfully used as bioactive compounds to attenuate restenosis. We investigated the effects of dexamethasone and dexamethasone-releasing biodegradable poly-D/L-lactic acid (PLA) stents/stent material in in vitro and in vivo models related to restenosis. Dexamethasone and dexamethasone-releasing PLA stents inhibited the production of mediators related to inflammation, fibrosis and endothelial activation, including TNF-a, IL-8, MCP-1, RANTES, TGF-P and VEGF in cell cultures. In addition, dexamethasone inhibited cell proliferation in vitro. PLA stent material induced a low-level inflammatory reaction (measured by antibody array method that detects 79 inflammatory factors) when introduced to macrophages in culture, and that was significantly attenuated by dexamethasone. Biocompatible testing of the stent material was carried out in rabbit dorsal muscle. In the bioactivity testing, intravascular dexamethasone releasing PLA stents induced minimal intimal hyperplasia as compared to non-drug-releasing PLA stents implanted in iliac arteries in the pig. Dexamethasone-releasing biodegradable stents may offer a promising new treatment option in PTA. However, further studies are needed to find out optimal concentrations and releasing profiles of dexamethasone and composition of biodegradable PLA material for the aimed therapeutic properties.