Preparation, characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS, phospholipase D inhibitor and doxorubicinPreparation, characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS, phospholipase

作     者：Maoyuan Song Yuanyuan Zhang Wenxi Zhang Guanghua Peng Jiaxing Wang Mengya Yin Jiajia Li Yajie Liu Xinru Li 宋茂远;张媛媛;张文茜;彭光华;王佳星;殷梦雅;李佳佳;刘雅婕;李馨儒

作者机构：Beijing Key Laboratory of Molecular Pharmaceuties and New Drug System＂ School of Pharmaceutical Sciences Peking University Health Science Center Beijing 100191 China 

出 版 物：《Journal of Chinese Pharmaceutical Sciences》 (中国药学（英文版）)

年 卷 期：2018年第27卷第5期

页      面：332-341页

核心收录：

学科分类：100702[医学-药剂学] 1007[医学-药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：The National Natural Science Foundation of China(Grant No.81541085) 

主　　题：Doxorubicin FIPI Liposomes α-TOS Tat 

摘      要：In the present study, we aimed to co-load the α-TOS conjugate Tat-TOS with the phospholipase D inhibitor FIPI and the antitumor drug doxorubicin（DOX） in a liposome delivery system for antitumor metastasis. Firstly, Tat-TOS was synthesized by solid-phase synthesis, and its structure was confirmed. The ability of free and liposomal Tat-TOS to induce apoptosis in vitro was evaluated by flow cytometry. Biodistribution of Tat-TOS-loaded liposomes was investigated by a molecular imaging system. Multi-component-loaded liposomes modified with Tat-TOS containing FIPI and DOX was prepared by thin film dispersion method in combination with p H gradient method and post-insertion method. Physicochemical properties were determined, and the in vitro uptake ability of the formulations was evaluated. The results showed that the prepared liposomes were characterized by a uniform particle size distribution and small particle size. The encapsulation efficiency of FIPI and DOX exceeded 85%. Both free and liposomal Tat-TOS significantly improved the activity of inducing apoptosis of tumor cells. The liposomes modified with Tat-TOS were apparently accumulated in normal lung tissue and tumor metastasized lung. Multi-component-loaded liposomes exhibited the strongest cell uptake capacity, suggesting a stronger anti-metastatic effect and anti-tumor activity in vivo.