In Vitro Cytotoxicity of Stealth Liposomes Co-encapsulating Doxorubicin and Verapamil on Doxorubicin-Resistant Tumor Cells(Pharmacology)
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概要
- 論文の詳細を見る
Multidrug resistance (MDR) is a major obstacle to successful clinical cancer chemotherapy. A novel doxorubicin anti-resistant Stealth liposomes (DARSLs), prepared by co-encapsulating doxorubicin (DOX) and verapamil (VER) into stealth liposomes, has been developed. The average particle size of DARSLs was 118.1±22.3nm. Encapsulation efficiencies of DOX and VER in DARSLs were greater than 95% and 70%, respectively. The IC_<50> of DARSLs as measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT) assay in multidrug resistant rat prostate cancer Mat-LyLu-B2 (MLLB2) cells was 0.079±0.017μM, 13 fold less than that for liposomal DOX with free VER (LDFV 0.96±0.46μM) but only about 2 times less than FDFV. The IC_<50> cytotoxicity on MLLB2 cells of the various formulations was as follows : DARSLs∿LDLV<FDFV<FDLV<LDFV<LD<FD, (LD : liposomal DOX; LV : liposomal VER; FD : free DOX; FV : free VER). Similar cytotoxicities were shown between DARSLs and FDFV in DOX-resistant human uterus sarcoma MES-SA/DX5 cells, reversing DOX-resistance to that shown by FD on DOX-sensitive MES-SA cells. For MLLB2 cells, DARSLs was the most cytotoxic, but its intracellular concentration of DOX, measured as mean cellular fluorescence with flow cytometry was lower (p<0.01) than that observed with the FDFV formulation. In conclusion, DARSLs was an effective DOX formulation which could overcome drug resistance in DOX-resistant tumor cells, but its mechanisms of action may be complex.
- 公益社団法人日本薬学会の論文
- 2005-05-01
著者
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ZHANG Qiang
School of Sciences, Southwest Petroleum University
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WANG Jian
Department of Radiology and Center for Advanced Medical Technology, Nippon Medical School
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LU Wan
School of Pharmaceutical Sciences, Peking University
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LEE How
Department of Pharmacology, National University of Singapore
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Zhang Qiang
School Of Pharmaceutical Sciences And State Key Laboratory Of Natural And Biomimetic Drugs Peking Un
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Wang Jian
Department Of Hematology And Oncology National University Hospital:school Of Pharmaceutics Sciences
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Zhang Qiang
School Of Pharmaceutics Sciences Peking University
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Lee How
Department Of Pharmacology National University Of Singapore
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GOH Boon
Department of Hematology and Oncology, National University Hospital
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CHANG Alex
Johns Hopkins-NUH International Medical Center
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LIU Xiao
School of Pharmaceutics Sciences, Peking University
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TAN Theresa
Department of Biochemistry, National University of Singapore
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Goh Boon
Department Of Haematology-oncology National University Hospital
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Goh Boon
Department Of Hematology And Oncology National University Hospital
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Tan Theresa
Department Of Biochemistry National University Of Singapore
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Wang Jian
Department Of Computational Science National University Of Singapore
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Lu Wan
School Of Pharmaceutics Sciences Peking University
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Wang Jian
Department Of Applied Biology & Chemical Technology The Hong Kong Polytechnic University
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Liu Xiao
School Of Pharmaceutics Sciences Peking University:johns Hopkins-nuh International Medical Center
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Wang Jian
Department Of Analytical Chemistry China Pharmaceutical University
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Lü Wanliang
School of Pharmaceutical Sciences, Peking University
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Wang JianCheng
Department of Hematology and Oncology, National University Hospital
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Goh BoonCher
Department of Hematology and Oncology, National University Hospital
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Liu Xiao
School of Environment, Tsinghua University
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