Abstract Title:

Combination of doxorubicin with harmine-loaded liposomes exerting synergistic antitumor efficacy.

Abstract Source:

Drug Dev Ind Pharm. 2018 Apr ;44(4):570-581. Epub 2018 Jan 9. PMID: 29260918

Abstract Author(s):

Jiongxi Lei, Shuangchen Cong, Maoyuan Song, Wenxi Zhang, Guanghua Peng, Xinru Li, Yan Liu

Article Affiliation:

Jiongxi Lei


CONTEXT: Long-circulation (PEGLip), pH-sensitive (PEOzLip), and active targeted liposomes (PEG-TATLip)-loading doxorubicin (DOX) and harmine (HM) were prepared. Their physicochemical properties and antitumor effect were investigated.

OBJECTIVES: The aims of the present study were to evaluate synergistic antitumor efficacy.

MATERIALS AND METHODS: Liposomes were prepared by using thin-film dispersion, active drug-loading and target post-insertion method. Subsequently physiochemical properties including particle size distribution, zeta potential, entrapment efficiency (EE), drug-loading content and in-vitro release were determined. Besides, the in vitro cytotoxicity of free drugs and drug-loaded liposomes was explored by using a Sulforhodamine-B Staining assay and the combination index values (CI Value) were calculated. Finally, the cellular uptake experiments by MCF-7cells were carried out via flow cytometry.

RESULTS AND DISCUSSION: All liposomes enhanced the antitumor effect significantly compared to free drugs. Among liposomes, PEG-TATLip enhanced the antitumor effect significantly compared to others. DOX and HM had moderate synergism with CI Value 0.85 for free drugs, 0.81 for PEGLip, 0.72 for PEOzLip, and 0.84 for PEG-TATLip respectively when the weight ratio of two drugs was 1:2. Moreover, the similarity between DOX and HM such as physicochemical properties, in vitro release modes and in vitro uptake kinetics characteristics when they were in the same formulations proved it possible for them to be delivered together.

CONCLUSION: Active targeting liposomes were the most effective delivery system as compared with pH-sensitive and long circulation liposomes. Additionally, DOX and HM could be co-delivered in liposomes and they could play moderate synergism effect in antitumor efficacy.

Study Type : In Vitro Study

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