目的 优化紫杉醇-油酸（PTX-OA）和鸦胆子油（BJO）分子配型组装纳米乳给药系统（PTX-OA/BJO CMNEs）的处方及制备工艺。方法 通过酯化反应制备得PTX-OA并建立检测PTX-OA的HPLC方法。采用超声乳化法制备PTX-OA/BJO CMNEs。单因素实验选出对PTX-OA/BJO CMNEs粒径影响较大的3个因素，L₁₆（4³） 正交试验以这3个因素油相质量浓度（A）、聚山梨酯-80用量（B）和超声功率（C）为考察因素，以平均粒径为评价标准，优选PTX-OA/BJO CMNEs的处方及制备工艺。对优选条件制备的PTX-OA/BJO CMNEs进行制剂学评价及体外细胞毒实验。结果 HPLC法检测PTX-OA在5～25 μg/mL线性关系良好，回归方程Y=12.709 X+6.252 0，r=0.999 5。最优处方为油相质量浓度为6.50 mg/mL，聚山梨酯-80-油相比例为3.5：6.5，超声乳化功率为120 W。制备的PTX-OA/BJO CMNEs外观良好，平均包封率为（100.6±1.9）%，平均粒径（108.7±2.3）nm，多分散系数（PDI）为0.232±0.038。透射电子显微镜（TEM）形态观察表明PTX-OA/BJO CMNEs粒径接近100 nm，分布较均一；其体外释放度在48 h达到67%。PTX-OA/BJO CMNEs溶液置于4 ℃，避光环境下保存60 d，包封率、粒径基本保持不变，稳定性较好。体外细胞毒实验显示，BJO与PTX-OA联用对HepG-2细胞生长抑制具有一定的协同作用。结论 优化后的PTX-OA/BJO CMNEs制备工艺简单易行，且药物之间具有增强细胞毒作用，为PTX和BJO联合用药的抗肿瘤作用机制的研究奠定了基础。

Objective To optimize the preparation method of paclitaxel-oleic acid (PTX-OA)/Brucea javanica oil (BJO) core- matched nanoemulsions (CMNEs). Methods PTX-OA/BJO was synthesized by esterification of PTX and OA, and determined by HPLC. Ultrasionic emulsification was used to prepare the PTX-OA/BJO CMNEs. The concentration of oil phase (A), quality of polysorbate 80 (B), and ultrasonic power (C) were selected as the significant factors after single-factor experiments and applied in L₁₆(4³) orthogonal array design with the average particle size as criterion. In addition, the physicochemical properties and cytotoxicity of PTX-OA/BJO CMNEs were tested. Results Linear range of PTX-OA was 5—25 μg/mL, Y = 12.709 X + 6.252 0, r = 0.999 5. The optimized conditions of PTX-OA/BJO CMNEs were as follows: The concentration of oil phase was 6.50 mg/mL, the mass ratio of polysorbate 80 to oil phase was 3.5:6.5 and the ultrasonic power was 120 W. The CMNEs prepared by the optimal conditions showed an entrapment efficiency of (100.6 ± 1.9)% and the nanoscale particle size was (108.7 ± 2.3) nm, PDI was 0.232 ± 0.038. The morphology of CMNEs examined by TEM exhibited a uniform and spherical shape. In vitro drug release was up to 67% after 48 h. After PTX-OA/BJO CMNEs sealed in a bottle were stored at 4 ℃ for 60 h, the average particle size and entrapment efficiency had no significant change. The cytotoxicity in vitro showed that the combined PTX-OA/BJO CMNEs could obviously inhibit the proliferation of HepG-2 cells. Conclusion The current study demonstrates the feasibility of incorporating PTX-OA and BJO into a single CMNEs for the synergism in cancer therapy. Furthermore, the preparation of PTX-OA/BJO CMNEs has the advantages of practicability and simple operation, as well lays the foundation for the further mechanism research of the combined paclitaxel and BJO in oncotherapy.

国家自然科学基金资助项目（81403109）；广东省科技计划项目（2016A020217017）；广东省卫生与计划生育委员会项目（A2015596）