目的 优化多西他赛长循环脂质体（DLCL）处方。方法 采用薄膜蒸发法制备DLCL，分别以卵磷脂（PC）与多西他赛（DOC）质量比（X₁）、PC与胆固醇（Chol）质量比（X₂）、DSPE-PEG 2000与PC物质的量之比（X₃）为考察对象，包封率（Y₁）、载药量（Y₂）、综合指标OD值为评价指标，采用Box-Behnken效应面法筛选DLCL的最佳处方。结果 最优处方为X₁＝0.616 2，X₂＝1.0，X₃＝?1.0；DLCL的包封率为（94.71±1.75）%，载药量为（5.37±0.43）%，标准偏差均小于10%；平均粒径139.6 nm，分布均匀，体外释放试验结果表明其具有明显的缓释效果。结论 采用Box-Behnken效应面法优化DLCL处方是有效、可行的。

Objective To optimize the formula of Docetaxel (DOC) long-circulation liposomes (DLCL). Methods DLCL was prepared by the membrane-hydration method. The effects of phosphatidylcholine (PC)-DOC (X₁), PC-cholesterol (Chol) (X₂), and the amount of DSPE-PEG 2000 (X₃) were observed. The encapsulation efficiency (Y₁), drug loading amount (Y₂), and the general requirements (Y₃) were evaluated and the formula was optimized by Box-Behnken design and response surface method. Results The optimal formula was as following: X₁＝0.616 2, X₂＝1.0, and X₃＝?1.0; The encapsulation efficiency was (94.71 ± 1.75)%, drug loading amount was (5.37 ± 0.43)%. The standard deviations were all below 10%. The average particle size was 139.6 nm. Moreover, in vitro release tests showed that the prepared DLCL had obvious sustained-release effects. Conclusion Using Box-Behnken design and response surface method to prepare DLCL is effective and feasible.

国家自然科学基金资助项目（30772790）