雷帕霉素药物洗脱支架的体外释放性能研究

目的：本文采用一种新型模拟心脏血流形态的药物释放装置来测定药物洗脱支架的体外释放性能。方法：以0.1%十二烷基硫酸钠作为释放介质，在（37±1）℃的条件下用新型药物释放装置模拟含药支架的体外释放性能。然后以ODS为固定相，以甲醇-乙腈-水（60∶16∶24）为流动相，在277 nm波长下用HPLC检测支架上雷帕霉素的残留量，来间接计算药物的释放率。结果：雷帕霉素在0.5~100 μg·mL^-1浓度范围线性良好，方法检出限为0.5 μg·mL^-1，回收率为98.8%~99.6%。药物释放呈现前快后慢的释放规律，在28 d后药物释放率达到82.8%，药物的释放机理符合扩散松弛机理与溶蚀机理相结合的综合模型。结论：该新型模拟心脏血流形态的药物释放装置具备含药支架体外药物释放性能研究的评估价值。

Objective: To evaluate in vitro drug release of drug-eluting stents with a simulating cardiovascular blood flow device.Methods: The release behavior of drug-eluting stent was evaluated with 0.1% SDS as release media at the temperature of(37±1)℃.The HPLC method was conducted on Agilent ODS column and detected with the wavelengths of 277 nm, the mobile phase consisted of methanol, acetonitrile and purified water(60:16:24).The residue amounts of rapamycin drug were determined by HPLC and the results were used to calculate the drug release rates.Results: In the linearity range of 0.5-100 μg·mL^-1, the correlation coefficient(r) was 1.000.The S/N was 24 for LOQ solution at 0.5 μg·mL^-1 level.The recoveries of rapamycin were within 98.8%-99.6%.The elution profile showed that drug release rate was decreasing gradually and the cumulative release rate was 82.8% for 28 days.The drug release mechanism of DESs was based on integrated model.Conclusion: The novel device can be used for monitoring drug release of DESs in vitro.

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