Preparation, characterization and evaluation of liposomal doxorubicin and harmine that show synergistic activity in vitro

doi:10.5246/jcps.2017.09.075

Abstract

Abstract:

A combinatory therapeutic system that simultaneously targets several independent pathways is preferred for the treatment of cancer. In our study, a combinatory liposomal delivery system containing doxorubicin (Dox) and harmine (HM) was constructed by thin film dispersing method together with pH gradient method. A simple, precise and accurate spectrophotometric method for the determination of Dox and HM in liposomal formulation was established and validated. A drug HSPC ratio of 1: 20, loading time of 30 min and loading temperature of 50 °C were the optimal conditions for the preparation of drug loaded liposomes, which exhibited excellent physicochemical properties such as average particle size of ~100 nm, low polydispersity index below 0.2 and high entrapment efficiency above 93%. Sustained release of drug from liposomes at pH 7.4 showed good biological safety. The synergetic cytotoxic effect for these two drugs was evaluated in MCF-7 cells. The in vitro antitumor studies demonstrated the superior anti-proliferation activity of the liposomal Dox and HM with a combination index of 0.81, which indicated great synergistic effect and increased anti-proliferation efficiency. The experimental data suggested that combinational liposome therapy could be an effective way to develop efficient treatment of cancers.

Key words: Doxorubicin, Harmine, Liposomes, Combination therapy, Synergistic effect

CLC Number:

R943

Supporting:

Jiongxi Lei, Shuangchen Cong, Maoyuan Song, Wenxi Zhang, Guanghua Peng, Yuanyuan Zhang, Mengya Yin, Jiaxing Wang, Jiajia Li, Xinru Li. Preparation, characterization and evaluation of liposomal doxorubicin and harmine that show synergistic activity in vitro[J]. Journal of Chinese Pharmaceutical Sciences, 2017, 26(9): 666-674.

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