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

doi:10.5246/jcps.2018.05.034

Abstract

Abstract:

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 pH 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.

Key words: Doxorubicin, FIPI, Liposomes, α-TOS, Tat

CLC Number:

R943

Supporting:

Maoyuan Song, Yuanyuan Zhang, Wenxi Zhang, Guanghua Peng, Jiaxing Wang, Mengya Yin, Jiajia Li, Yajie Liu, Xinru Li. Preparation, characterization and evaluation of multi-component-loaded liposomes containing Tat-TOS, phospholipase D inhibitor and doxorubicin[J]. Journal of Chinese Pharmaceutical Sciences, 2018, 27(5): 332-341.

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