雷帕霉素缓释涂层支架在模拟心脏泵血状态下的体外释药研究

 目的利用体外模拟血循环装置,评价自制雷帕霉素乳酸-羟基乙酸共聚物(PLGA)涂层支架的体外药物释放规律,探讨释药机制,为涂层支架的应用提供药动学参数。方法以316L不锈钢为支架,采用高压多层电喷技术制备含雷帕霉素的PL-GA涂层。采用自制体外模拟循环装置,定时取样,RP-HPLC检测残留于支架的药物,评价流体循环冲刷状态下雷帕霉素涂层支架的药物释放度。结果自制雷帕霉素PLGA涂层支架的涂层厚度平均为5～10μm,雷帕霉素的平均含量为14.39μg。在模拟流体循环冲刷状态下,雷帕霉素涂层支架的体外药物释放呈先快后慢的趋势,12和30d药物累积释放百分率分别为(58.48±5.67)%和(60.66±5.75)%,释药机制以溶蚀为主。结论体外模拟血循环装置适于药物涂层支架体外释药的研究;自制雷帕霉素PLGA涂层支架的体外释药符合内皮细胞增殖规律,与动物体内疗效一致。

In Vitro Release of Rapamycin Sustained Eluting Stent Detected by a New Designed Circulating Device

OBJECTIVE To detect in vitro release properties of rapamycin sustained eluting stent and to provide pharmacokinetic profile for clinical application.METHODS Rapamycin and PLGA were coated on the 316L stainless metal stent by the high pressure multilayer electronic spraying technique.The in vitro release kinetics of rapamycin sustained eluting stent were studied by a self-designed mimic cardiac pumping device.At the interval,the concentration of rapamycin on the remained stent was detected by RP-HPLC method.RESULTS The average thickness of rapamycin and PLGA coating was 5～10 μm and the average content of rapamycin was 14.39 μg.The in vitro release profile showed that rapamycin released slowly from the coating with the fast speed at the early stage and slow speed at the later stage.The cumulative release percentages were(58.48±5.67)% for 12 d and(60.66±5.75)% for 30 d.The release mechanism accorded to Hixson-Crowell erosion model.CONCLUSION The self-designed device for mimic cardiac pumping is suitable to study the in vitro release of drug eluting stent.And the prepared rapamycin sustained eluting stent shows a good control release profile according with the proliferation of vascular smooth muscle cells.