目的 针对柠檬苦素（limonin，LM）的成药性问题，开发其脂质体制剂，优化处方和制备工艺，并考察其体外抗肿瘤活性。方法 采用薄膜分散法制备柠檬苦素脂质体（LM@Lip），通过单因素实验和正交试验筛选LM@Lip的制备工艺和处方，采用Malvern粒度仪检测所制备LM@Lip粒径、PDI及Zeta电位，采用HPLC检测其包封率和载药量，透析法研究LM@Lip体外释放情况，MTT法评价LM@Lip对HepG2及A549细胞的毒性。结果 优化后的脂质体制备条件：药脂比为1：150，胆脂比为1：9，探头超声条件为功率120 W、时间6 min（间隔1 s）。载药脂质体的平均粒径为（119.5±6.2）nm，PDI为0.318±0.124，Zeta电位为（-17.2±1.3）mV，包封率为87.9%，载药量为0.57%，药物质量浓度为63.4 μg/mL。体外释放实验结果显示，12 h累积释放量为58.59%。MTT结果显示，LM@Lip对HepG2和A549细胞的半数抑制浓度（IC₅₀）分别为20.16、15.39 μg/mL，其肿瘤抑制作用优于LM单药。结论 将LM制备成LM@Lip可以增加药物的稳定性及溶解度，药物表现出一定的缓释现象，并且能明显抑制肿瘤细胞增殖，效果优于LM。

Objective In view of druggability issue of limonin (LM), the liposomal preparation was developed. The liposomal formulation and preparation process were optimized, and its in vitro antitumor activity was investigated. Methods In this study, LM was loaded in liposomes to increase its stability and solubility. Meanwhile, in vitro cytotoxicity of LM@Lip was evaluated. LM@Lip were prepared by thin-film dispersion method, and formulation selection and process optimization were operated by single factor and orthogonal experiment. Size distribution, PDI and zeta potential were measured by Malvern sizer, and the encapsulation efficiency and drug loading content were determined by HPLC. The dialysis method was used to investigate the release profile of LM@Lip. In vitro cytotoxicity against HepG2 and A549 cells were estimated by MTT method. Results The optimized preparation conditions of liposomes were as follows:drug/lipid ratio was 1:150, cholesterol/lipid ratio was 1:9, the ultrasonic power was 120 W for 6 min (1 s interval). The average particle size, PDI and Zeta potential of optimized LM@Lip were (119.5±6.2) nm, 0.318±0.124, (-17.2±1.3) mV, respectively, and the encapsulation efficiency and drug loading content were 87.9% and 0.57%. The final concentration of LM was 63.4 μg/mL. The release results showed 58.59% drug was released in 12 h. MTT results showed that the IC₅₀ of LM@Lip on HepG2 and A549 cells was 20.16 and 15.39 μg/mL, respectively, and its in vitro antitumor was superior to that of LM. Conclusion Liposomes can increase the stability and solubility of LM. LM@Lip showed slow-release profile and significant tumor inhibition superior to LM.

国家自然科学基金资助项目（81503259）；江苏省自然科学基金资助项目（BK20151002）；中国科协青年人才托举工程项目（CACM-2017-QNC1-01）；江苏省六大人才高峰项目（SWYY-057）；江苏省研究生科研与实践创新计划项目（KYCX18_1614）；大学生实践创新训练计划项目（201810315029Z）