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

载阿霉素-芦米司匹多囊脂质体的制备及体内外评价

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 3–8μm 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.

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3–8μm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。