目的 制备水飞蓟素脂质体（silymarin liposomes，SM-L）并进行质量评价，考察SM-L对人永生化角质形成细胞（human immortal keratinocyte line，HaCaT）增殖和摄取的影响。方法 采用乙醇注入法制备SM-L，以包封率和ζ电位为考察指标，Box-Behnken响应曲面设计实验优化SM-L处方和制备工艺，并对SM-L进行质量评价；采用噻唑蓝（MTT）法考察SM-L对HaCaT细胞增殖的影响，细胞划痕实验考察SM-L对HaCaT细胞水平迁移能力的影响，共聚焦显微镜观察并以流式细胞术考察HaCaT细胞对SM-L的摄取情况。结果 优化的SM-L制备工艺为大豆磷脂、水飞蓟素和胆固醇的质量比为20∶7.94∶6.21，无水乙醇和水的最佳比例为1∶10。SM-L包封率为（85.44±0.87）%，平均粒径为（133.80±2.13）nm，多分散指数为0.134±0.020，ζ电位为（−14.1±0.3）mV，稳定性良好，36 h皮肤透过率为（14.58±6.37）%，皮肤滞留率为（65.80±4.04）%。细胞实验证明一定质量浓度范围的SM-L能促进HaCaT细胞增殖，SM-L相比水飞蓟素对HaCaT细胞的水平迁移促进作用有明显提高，并且SM-L能够有效提高HaCaT细胞对水飞蓟素的摄取。结论 制备所得的SM-L粒径均一，性质稳定，透皮性能好，并且可以促进HaCaT细胞增殖和对水飞蓟素的摄取，有很好的角质修复作用。

Objective Silymarin liposomes (SM-L) were prepared and evaluated to investigate its effect on the uptake and migration of HaCaT cells. Methods SM-L was prepared by ethanol injection method. Taking the entrapment efficiency and ζ potential as the indexes, the Box-Behnken response surface design was used to optimize the best formulation and process of SM-L, and the quality of SM-L was evaluated; MTT method was used to investigate the effect of SM-L on the proliferation of HaCaT cells, cell scratch test was used to investigate the effect of SM-L on the horizontal migration ability of HaCaT cells, confocal microscope and flow cytometry were used to investigate the uptake of SM-L by HaCaT cells. Results The best preparation process of SM-L was as follows: the mass ratio of soybean phospholipid, silymarin (SM-L) and cholesterol was 20:7.94:6.21, and the optimum ratio of organic phase and aqueous phase was 1:10. The entrapment efficiency of SM-L was (85.44 ± 0.87)%, the particle size was (133.80 ± 2.13) nm, the polydispersity index was 0.134 ± 0.020, the ζ potential was (−14.1 ± 0.3) mV, the skin transdermal rate was (14.58 ± 6.37)%, and skin retention rate was (65.80 ± 4.04)% within 36 h, and SM-L had good stability. Cell experiments showed that SM-L in a certain concentration range could promote the proliferation of HaCaT cells. Compared with silymarin, SM-L could significantly improve the horizontal migration of HaCaT cells, and SM-L could effectively improve the uptake of silymarin by HaCaT cells. Conclusion The prepared SM-L has uniform particle size, good stability and transdermal performance, can promote HaCaT cell proliferation and silymarin uptake, and has a good role in cuticle repair.

R283.6

国家自然科学基金资助项目（82003985）；吉林省教育厅科学技术研究项目（JJKH20210995KJ）；吉林省科技发展计划项目（20210204013YY）