Epi-1修饰的表阿霉素/姜黄素脂质体处方优选及细胞毒性考察  

Formulation Optimization and Cytotoxicity Investigation of Epi-1 Modified Epirubicin/Curcumin Liposomes

作　　者：王宇佳 张新悦 严德康 耿宏侠 于英杰 吴亚男[1] 郭睿博 李学涛[1] 吕佳[1] WANG Yujia;ZHANG Xinyue;YAN Dekang;GENG Hongxia;YU Yingjie;WU Yanan;GUO Ruibo;LI Xuetao;LYU Jia(College of Pharmacy,Liaoning University of Traditional Chinese Medicine,Dalian 116600,Liaoning,China)

机构地区：[1]辽宁中医药大学药学院,辽宁大连116600

出　　处：《辽宁中医药大学学报》2022年第6期53-56,共4页Journal of Liaoning University of Traditional Chinese Medicine

基　　金：国家自然科学基金(81874347)。

摘　　要：目的优化Epi-1修饰的表阿霉素/姜黄素脂质体处方,并考察其对人卵巢癌细胞SKOV3的体外毒性。方法薄膜分散法-硫酸铵水化法制备Epi-1修饰的表阿霉素/姜黄素脂质体。以包封率为指标,采用Box-Behnken响应面法优化处方中卵磷脂/胆固醇(EPC/Chol)质量比、超声功率、卵磷脂/姜黄素(EPC/Cur)质量比,HPLC法测定包封率。体外考查空白脂质体、表阿霉素/姜黄素脂质体、Epi-1修饰的表阿霉素/姜黄素脂质体作用于人卵巢癌SKOV3细胞后对存活率的影响。结果优化后脂质体处方为EPC/Chol质量比为9(mg/mg),超声功率为600 W,EPC/Cur质量比为112(mg/mg),测定三批脂质体中两药的平均包封率,结果为(92.16±1.20)%(n=3)。体外细胞毒性考查结果显示,Epi-1修饰的表阿霉素/姜黄素脂质体对人卵巢癌SKOV3细胞的抑制效果强于表阿霉素/姜黄素脂质体(P<0.05),膜材无细胞毒性。结论成功制备Epi-1修饰的表阿霉素/姜黄素脂质体处方,修饰的Epi-1增强了表阿霉素/姜黄素脂质体对人卵巢癌细胞主动靶向性,细胞毒性强于表阿霉素/姜黄素脂质体。Objective To Optimization of Epi-1 modified epirubicin/curcumin liposomes formulation and examination of its toxicity to human ovarian cancer cells SKOV3 in vitro.Methods Preparation of Epi-1 modified epirubicin/curcumin liposomes by thin film dispersion-ammonia sulfate hydration method.Using the encapsulation rate as the index,the lecithin/cholesterol(EPC/Chol)mass ratio,ultrasonic power,lecithin/curcumin(EPC/Cur)mass ratio in the formulation were optimized by the central composite design-response surface method and the encapsulation rate was determined by HPLC.The effects of blank liposomes,epirubicin/curcumin liposomes,and Epi-1 modified epirubicin/curcumin liposomes on the survival rate of human ovarian cancer SKOV3 cells were investigated in vitro.Results The liposome formulation was optimized for an EPC/Chol mass ratio of 9(mg/mg),ultrasonic power of 600 W,and an EPC/Cur mass ratio of 112(mg/mg).The optimized liposome formulation was EPC/Chol mass ratio of 9(mg/mg),ultrasonic power of 600 W,and EPC/Cur mass ratio of 112(mg/mg),and the liposome encapsulation rate was determined for three batches with an average of(92.16±1.20)%(n=3).The results of in vitro cytotoxicity examination showed that Epi-1 modified epirubicin/curcumin liposomes inhibited human ovarian cancer SKOV3 more effectively than epirubicin/curcumin liposomes(P<0.05),and the membrane materials were not cytotoxic.Conclusion The Epi-1 modified epirubicin/curcumin liposomes formulation was successfully prepared,and the modified Epi-1 enhanced the active targeting of epirubicin/curcumin liposomes to human ovarian cancer cells with stronger cytotoxicity than epirubicin/curcumin liposomes.

关 键 词：Epi-1 脂质体 表阿霉素 姜黄素 Box-Behnken响应面法 细胞毒性 

分 类 号：R284.2[医药卫生—中药学]