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    响应面法优化依托泊苷脂质体制备工艺的研究

    Formulation Optimization of Etoposide Loaded Liposomes by Response Surface Methodology

      摘要
    • 摘要: 目的 制备依托泊苷脂质体并考察其药剂学性质。方法 采用薄膜水化-高压均质法制备依托泊苷脂质体，以胆固醇与氢化磷脂的摩尔比(A)、脂质体溶液中的磷脂浓度(B)、依托泊苷与氢化磷脂的质量比(C)为考察因素，以包封率(Y1)、载药量(Y2)、综合指标(Y3)为响应值，经Box-Behnken效应面法(response surface methodology，RSM)进行处方优化，得到最优处方，并测定脂质体的粒径。结果 经RSM优化后，A、B、C分别为0.49，4.96%，0.15；制得的依托泊苷脂质体实测包封率为82.6%，载药量为11.4%，平均粒径为132.5 nm。结论 利用Box-Behnken效应面法优化依托泊苷脂质体处方，能制备符合药剂学要求的脂质体，可供体内实验研究。

       

      Abstract: OBJECTIVE To prepare etoposide liposomes and optimize the preparation parameters. METHODS Box-Behnken design was employed to optimize the cholesterol-hydrogenated phospholipids(A), phospholipid concentration of liposome solution(B) and the ratio of etoposide liposomes to hydrogenated phospholipids(C) to obtain a high entrapment efficiency(Y1), loading content(Y2), and overall desirability (Y3) of etoposide liposomes by the film-dispersion method with high pressure homogenization. RESULTS The optimum conditions were A of 0.49, B of 4.96% and C of 0.15. Under these conditions, the entrapment efficiency was 82.6%, loading content was 11.4% and the average particle size was 132.5 nm. CONCLUSION Box-Behnken design plays an important role in optimization experiments leading to robust results supporting high quality of etoposide liposomes.

       

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