期刊
DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY
卷 42, 期 1, 页码 136-149出版社
TAYLOR & FRANCIS LTD
DOI: 10.3109/03639045.2015.1036066
关键词
Ovarian cancer; ovcar-3; paclitaxel; thermo-sensitive liposomes; topotecan
资金
- University Grant Commission (UGC), Delhi as Junior Research Fellowship (JRF)
Context: Synergistically active combinations have been used to enhance therapeutic efficacy for ovarian cancer chemotherapy.Objective: The synergistically active combination of paclitaxel-topotecan (Pac-Top; 20:1, w/w) were loaded into folate-anchored PEGylated liposomes (FPL-Pac-Top) for safe and effective treatment of ovarian cancer.Materials and methods: Coupling reactions were carried out using carbodiimide chemistry and confirmed by infrared spectral analysis. These liposomes were studied for shape and physical interaction (and integrity), in vitro drug release kinetics, hemolytic toxicity, ex vivo pharmacodynamics in OVCAR-3 cell lines, and pharmacokinetics in ovarian tumor-bearing mice.Results: The differential scanning calorimeter studies exhibited melting of liposomes (approximate to 150nm) at approximate to 41 degrees C. The drug(s) release from liposomes followed Fickian diffusion model. The hematological studies revealed insignificant toxicity to blood cells. In vivo studies showed long circulatory behavior (increased AUC(0-t) and AUMC(0-t) and MRT) and selective accumulation of FPL-Pac-Top in the ovaries. FPL-Pac-Top showed less necrosis and more apoptosis in flow cytometry. Kaplan-Meier survival analysis revealed the doubling of the survival time with FPL-Pac-Top in comparison to Pac-Top solution.Discussion and conclusion: Potentiated anti-cancer activity of FPL-Pac-Top was attributed to multiple features viz. thermosensitivity, long circulatory nature and targetability. Such approach could be a paradigm chemotherapeutic approach for safe and effective targeting of cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据