载阿霉素-芦米司匹多囊脂质体的制备及体内外评价

doi:10.5246/jcps.2021.09.061

中国药学(英文版) ›› 2021, Vol. 30 ›› Issue (9): 736-742.DOI: 10.5246/jcps.2021.09.061

载阿霉素-芦米司匹多囊脂质体的制备及体内外评价

刘雅婕, 王雨, 李佳佳, 许晓庆, 李馨儒^*()

北京大学医学部?药学院?分子药剂学与新释药系统北京市重点实验室, 北京 100191

收稿日期:2021-05-14 修回日期:2021-07-18 接受日期:2021-08-06 出版日期:2021-09-27 发布日期:2021-09-27
通讯作者: 李馨儒
作者简介:
+ Tel.: +86-10-82801508 , E-mail: ll@bjmu.edu.cn

Preparation and evaluation of doxorubicin-luminespib co-loaded multivesicular liposomes

Yajie Liu, Yu Wang, Jiajia Li, Xiaoqing Xu, Xinru Li^*()

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug System; School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China

Received:2021-05-14 Revised:2021-07-18 Accepted:2021-08-06 Online:2021-09-27 Published:2021-09-27
Contact: Xinru Li

摘要/Abstract

摘要：

将不同靶点的化疗药物制成共递送系统非常适用于肿瘤治疗, 因此本研究将阿霉素与芦米司匹两种化疗药物制成共递送的多囊脂质体。首先建立了简单而准确的双波长紫外分光光度法测定脂质体中阿霉素和芦米司匹的包封率。采用复乳溶剂挥发法成功制备载阿霉素和/或芦米司匹多囊脂质体, 粒径在3–8 μm之间, 阿霉素与芦米司匹的包封率分别达到95%和73%以上。脂质体制剂中两个药物的协同性用MDA-MB-231细胞的细胞毒实验评价。研究结果表明, 包载阿霉素和芦米司匹的多囊脂质体协同指数达到0.43, 表明具有显著的协同效应, 可进一步增强体外抗增殖抑制作用活性。所有实验结果表明, 上述包载阿霉素与芦米司匹的共递送多囊脂质体可成为有效的肿瘤治疗手段。

关键词: 阿霉素, 芦米司匹, 多囊脂质体, 组合治疗, 协同效应

Abstract:

A combinational therapeutic system that simultaneously administrates various pathways is preferred for anti-cancer treatment. In the present study, we successfully constructed a co-delivery system, multivesicular liposomes (MVLs) co-encapsulating doxorubicin (DOX) and luminespib (AUY922). A simple and accurate dual-wavelength spectrophotometric method was established for the determination of DOX and AUY922 in liposomal formulation. MVL-loading drugs were prepared by a multi-emulsion solvent evaporation method, which exhibited excellent physicochemical properties, such as particle size of 3–8 μm and high entrapment efficiency above 95% for DOX and 73% for AUY922. The synergetic cytotoxic effect for these two drugs was evaluated in MDA-MB-231 cells. The in vitro antitumor studies demonstrated the superior anti-proliferation activity of DOX and AUY922 with a combination index of 0.43, indicating a great synergistic effect. The experimental data suggested that combinational use of DOX and AUY922 within liposomes could be an effective way to develop efficient treatments of cancers.

Key words: Doxorubicin, Luminespib, Multivesicular liposomes, Combination therapy, Synergistic effect

Supporting:

刘雅婕, 王雨, 李佳佳, 许晓庆, 李馨儒. 载阿霉素-芦米司匹多囊脂质体的制备及体内外评价[J]. 中国药学(英文版), 2021, 30(9): 736-742.

Yajie Liu, Yu Wang, Jiajia Li, Xiaoqing Xu, Xinru Li. Preparation and evaluation of doxorubicin-luminespib co-loaded multivesicular liposomes[J]. Journal of Chinese Pharmaceutical Sciences, 2021, 30(9): 736-742.

图/表 7

Figure 1. Chemical structural of DOX and AUY922.

Figure 2. Ultraviolet spectra of blank MVLs (black line), DOX (red line), and AUY922 (blue line).

Table 1. The parameters of regression equations.

Figure 3. Microscopic photographs (40 × 10) of blank MVLs (A), D/MVLs (B), A/MVLs (C), and DA/MVLs (D).

Table 2. Average particle size and D90 of MVLs.

Table 3. The IC50 values of free DOX, free AUY922, and MVLs encapsulating DOX and/or AUY922 against MDA-MB-231 cells.

Figure 4. Cytotoxicity of free DOX, free AUY922, DOX, and/or AUY922 co-loaded MVLs against MDA-MB-231 cells.

参考文献 9

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载阿霉素-芦米司匹多囊脂质体的制备及体内外评价

Preparation and evaluation of doxorubicin-luminespib co-loaded multivesicular liposomes

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