Page 25 - 2020年21期

穿膜肽 GGPFV 修饰的柔红霉素/薯蓣皂苷脂质体的处方优化及

细胞毒性研究 Δ

＊
姚雪敏 ，荆 鸣，蔡馥伊，孔 亮，李学涛（辽宁中医药大学药学院，辽宁 大连 116600）
#
中图分类号 R283.6 文献标志码 A 文章编号 1001-0408（2020）21-2579-06
DOI 10.6039/j.issn.1001-0408.2020.21.04

摘 要 目的：制备穿膜肽GGPFV修饰的柔红霉素/薯蓣皂苷脂质体，对其处方进行优化，并初步评价其对乳腺癌细胞的体外毒
性。方法：采用薄膜分散法和硫酸铵水化法，将柔红霉素和薯蓣皂苷包载其中，在表面以聚乙二醇-二硬脂酰基磷脂酰乙醇胺2000
（DSPE-PEG2000 ）-GGPFV修饰，制备GGPFV修饰的柔红霉素/薯蓣皂苷脂质体。以包封率为指标，采用Box-Behnken响应面法优化
处方中水化体积、胆固醇用量和柔红霉素用量；测定按最优处方制备的 3 批脂质体的包封率。比较柔红霉素/薯蓣皂苷脂质体、
GGPFV修饰的柔红霉素/薯蓣皂苷脂质体和空白脂质体作用后对人乳腺癌MDA-MB-435S细胞存活率的影响。结果：最优处方为
水化体积 5 mL、胆固醇 4 mg、蛋黄卵磷脂 22 mg、柔红霉素 0.55 mg、薯蓣皂苷 0.85 mg、DSPE- PEG2000 3.5 mg、DSPE-PEG2000-GGP-
FV 2 mg。所制3批脂质体中，柔红霉素的包封率为（96.21±1.54）％，薯蓣皂苷的包封率为（95.39±2.48）％。体外细胞毒性试验
显示，GGPFV 修饰的柔红霉素/薯蓣皂苷脂质体对 MDA-MB-435S 细胞的抑制作用显著强于柔红霉素/薯蓣皂苷脂质体（P＜
0.05），膜材无细胞毒性。结论：成功制得GGPFV修饰的柔红霉素/薯蓣皂苷脂质体，其对人乳腺癌MDA-MB-435S细胞的体外抑
制作用明显增强。
关键词 脂质体；GGPFV；柔红霉素；薯蓣皂苷；处方优化；Box-Behnken响应面法；细胞毒性

Formulation Optimization and Cytotoxicity Study of GGPFV-modified Daunorubicin/dioscin Liposomes
YAO Xuemin，JING Ming，CAI Fuyi，KONG Liang，LI Xuetao（School of Pharmacy，Liaoning University of
TCM，Liaoning Dalian 116600，China）

ABSTRACT OBJECTIVE：To prepare GGPFV-modified Daunorubicin/dioscin liposomes，and to optimize their formulation and
to preliminarily evaluate their cytotoxicity to breast cancer cells in vitro. METHODS：Daunorubicin and diosgenin were wrapped by
thin film dispersion method and ammonium sulfate hydration method；the surface was modified with DSPE-PEG2000-GGPFV to
prepare GGPFV-modified Daunorubicin/dioscin liposomes. Taking encapsulation rate as index，Box-Behnken response surface
methodology was used to optimize the film hydration volume，cholesterol amount and daunorubicin amount in the formulation. The
entrapment efficiency of 3 batches of liposomes prepared according to the optimal formulation was determined. The effects of
Daunorubicin/dioscin liposomes，GGPFV-modified Daunorubicin/dioscin liposomes and blank liposomes on the survival rate of
human breast cancer MDA-MB-435S cells were compared. RESULTS：The optimal formulation was as film hydration volume of 5
mL，cholesterol of 4 mg，yolk lecithin of 22 mg，daunorubicin of 0.55 mg，dioscin of 0.85 mg，DSPE-PEG2000 of 3.5 mg，
DSPE-PEG2000-GGPFV of 2 mg. The encapsulation rate of daunorubicin was（96.21±1.54）％ and that of dioscin was（95.39±
2.48）％ in the 3 batches of liposomes prepared. The in vitro cytotoxicity tests showed that the inhibition effect of GGPFV-modified
Daunorubicin/dioscin liposome on MDA-MB-435S cells was significantly stronger than that of Daunorubicin/dioscin liposome（P＜
0.05）. There was no cytotoxicity in the membrane. CONCLUSIONS： GGPFV-modified Daunorubicin/dioscin liposomes are
successfully prepared，and its inhibitory effect on human breast cancer MDA-MB-435S cells in vitro was significantly enhanced.
KEYWORDS Liposome；GGPFV；Daunorubicin；Dioscin；Formulation optimization；Box-Behnken design response surface
methodology；Cytotoxicity

柔红霉素是一种蒽环类抗肿瘤抗生素，易溶于水且 等 [1-2] 。柔红霉素的抗癌机制主要是其经肝脏代谢可生
水溶液性质稳定，被广泛用于治疗急性白血病、慢性粒 成柔红霉素醇，后者可通过嵌入癌细胞 DNA 碱基对来
细胞性白血病、恶性淋巴瘤、非小细胞肺癌、乳腺癌 改变DNA拓扑状态，并可通过抑制DNA聚合酶活性及

Δ 基金项目：国家自然科学基金资助项目（No.81874347） 损伤DNA来影响基因表达，从而达到杀伤肿瘤细胞、治
＊硕士研究生。研究方向：新型给药系统。电话：0411-85890145。 疗癌症的目的 。但是，柔红霉素在临床上表现出骨髓
[3]
E-mail：1106827103@qq.com
抑制、心肌损伤、胃肠道刺激、肝肾损伤及局部组织坏死
# 通信作者：教授，博士生导师。研究方向：新型给药系统。电
话：0411-85890145。E-mail：Lixuetao1979@163.com 等明显的毒副作用，故有研究者将其包裹在脂质体内核

中国药房 2020年第31卷第21期 China Pharmacy 2020 Vol. 31 No. 21 ·2579 ·