关键词: 阿霉素, 去氢骆驼蓬碱, 脂质体, 组合治疗, 协同效应

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