聚乳酸-羟基乙酸载利福喷丁微球的体外释放机制研究

In vitro release of rifapentine from poly（lactic acid-co-glycolic acid） microspheres

摘要:

目的：探讨聚乳酸-羟基乙酸载利福喷丁微球体外释放机制。方法：采用乳化-溶剂挥发法制备不同载药量的聚乳酸-羟基乙酸载利福喷丁微球，于PBS缓冲溶液（0.2 mol/L，pH7.4）中测定微球体外释放量，对释放曲线进行零级方程拟合、一级方程拟合和 Higuchi方程拟合。结果：聚乳酸-羟基乙酸载利福喷丁微球的载药量分别为（8.04±0.29）%、（17.16±0.40）%和（23.93±0.48）%，差异有统计学意义（F=1 195.325，P=0.000）。微球呈球形，分散性良好，药物均匀地分布于载体基质中。载药微球在前2 d释放药物较快，累计释放药物量分别为（9.07±0.11）%、（13.33±0.04）%和（15.5±0.09）%，差异有统计学意义（F=4 414.474，P=0.000）。从第3天开始，释放药物速率减缓，总累计释放量分别为（72.10±0.26）%、（80.22±0.56）%和（78.60±0.63）%，差异有统计学意义（F=212.916，P=0.000）。在3种拟合方程中，均以Higuchi方程的相关系数更接近于1。结论：聚乳酸-羟基乙酸载利福喷丁微球体外释放呈突释和缓释两相释放，释放曲线更符合Higuchi方程释放规律。

Abstract:

Objective：To investigate the in vitro release mechanism of rifapentine-loaded poly（lactic-co-glycolic acid）（PLGA） microspheres. Methods：Rifapentine-loaded PLGA microspheres were prepared by the emulsification-solvent evaporation method. The in vitro release tests were carried out in phosphate buffer solution（0.2 mol/L，pH7.4），and the in vitro release profiles were prescribed by the zero-level equation，one-level equation and Higuchi equation，respectively. Results：Rifapentine-loaded PLGA microspheres were successfully prepared with drug loading of （8.04±0.29）%，（17.16±0.40）% and （23.93±0.48）%（F=1 195.325，P=0.000）. The microspheres were spherical particles with good dispersion. Rifapentine was evenly distributed in the PLGA matrix. The drug release was faster during the first two days and the cumulative drug releases of the three rifapentine-loaded PLGA microspheres were （9.07±0.11）%，（13.33±0.04）% and （15.5±0.09）%（F=4 414.474，P=0.000），which slowed down from the third day. The total cumulative drug releases were （72.10±0.26）%，（80.22±0.56）% and （78.60 ± 0.63）%（F=212.916，P=0.000）. The correlation coefficients of the Higuchi equation were closer to 1 among that of the three fitting equations. Conclusion：Rifapentine-loaded PLGA microspheres exhibit an initial burst followed by a period of slow release in vitro，and the release profiles is more consistent with the Higuchi equation.