维生素A-姜黄素脂质体的制备及细胞毒性研究

 目的 制备肝星状细胞靶向维生素A-姜黄素脂质体（VA-CUR-L），并进行体外细胞毒性实验。方法 采用逆相蒸发法制备VA-CUR-L，测定其包封率及VA结合率；脂质体分别在4，25 ℃下密闭放置30d，以包封率、VA结合率及过氧化值为指标考察其稳定性；以视黄醇结合蛋白受体高表达的鼠肝星状细胞HSC-T6和无视黄醇结合蛋白受体表达的人食管癌细胞A-549为细胞模型，采用MTT法考察该脂质体的细胞毒性及靶向性。结果 脂质体平均包封率为89.32%，VA结合率为61.34%；脂质体于4 ℃贮存较稳定；细胞实验显示，游离姜黄素、姜黄素脂质体及VA-CUR-L对HSC-T6的IC₅₀值分别为31.53，14.95和8.28 μg·mL-1 ，姜黄素脂质体和VA-CUR-L对A-549细胞作用相当。结论 在最佳工艺条件下制得的VA-CUR-L包封率高、稳定性好，且可特异性靶向作用于肝星状细胞，提高药物疗效。

Study on Preparation of Vitamin A-Curcumin Liposome and Its Cytotoxicity

OBJECTIVE To prepare Hepatic stellate cell targeting Vitamin A-curcumin liposome and to investigate its cytotoxicity in vitro. METHODS Reverse phase evaporation was used to prepare VA-curcumin liposome and the entrapment efficiency and the VA binding rate was determined. Entrapment efficiency， VA binging rate and peroxide value were determined to evaluate the stability of liposome at 4 and 25 ℃ for 30 d. MTT assay was used to investigate the cytotoxicity and targeting ability of the liposome in rat hepatic stellate cells HSC-T6 with high expression of retinol binding protein and human esophageal cancer cells A-549 without expression of retinol binding protein. RESULTS The average entrapment efficiency for curcumin was 89.32%， and binding rate for VA was 61.34%. The liposome stored at 4 ℃ was stable. The RESULTS of MTT assay showed that IC₅₀ of curcumin， curcumin liposome， and VA-curcumin liposome in HSC-T6 cell were 31.53， 14.95 and 8.28 μg·mL-1， respectively. Curcumin liposome and VA-curcumin liposome had same cytotoxic effects in A-549 cell. CONCLUSION The optimized conditions were obtained with high entrapment efficiency and good stability. VA-curcumin liposome could specifically target HSC and promote therapeutic effect of curcumin.