A Pegylated Liposomal Platform : Pharmacokinetics, Pharmacodynamics, and Toxicity in Mice Using Doxorubicin as a Model Drug
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概要
- 論文の詳細を見る
Aims were to observe pharmacokinetics, pharmacodynamics, and toxicity for constructing a Sino-pegylated liposomal platform. Human hepatocarcinoma cells (Bel7402) and murine hepatocarcinoma cells (H22) were used for the cytotoxicity assay and the in vivo solid xenograft tumor model in mice, respectively. Pharmacokinetic results in mice showed that the pegylated liposomal doxorubicin markedly prolonged the blood circulation of doxorubicin. Elimination half-time (T1/2,γ) of pegylated, regular liposomal doxorubicin and free doxorubicin were 46.09 ± 14.44, 26.04 ± 3.34, and 23.72 ± 5.13 h, respectively. The area under the concentration-time curves (AUC0–∞) (h · μg/g) of the pegylated and regular liposomal doxorubicin were 6.8- and 2.6-fold higher than that of free doxorubicin, respectively. Cytotoxicity and antitumor activity in vivo indicated that activity of the pegylated liposomal doxorubicin was higher than that of the regular or the free one, respectively. After two weeks of tail intravenous injection of the pegylated liposomal doxorubicin at a single dose of 10 mg/kg, no significant damage was observed in gastric, intestinal mucosa, and heart muscle, but pronounced damages were found in the control group after dosing free doxorubicin. The results demonstrate that the pegylated liposomes improve the efficacy of toxics and reduce the toxicity, therefore providing favorable evidence for building a pegylated liposomal platform.
- 社団法人 日本薬理学会の論文
- 2004-07-20
著者
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Wang Li
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Qiang
中華人民共和国
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Zhang Q
State Key Laboratory Of Natural And Biomimetic Drugs And School Of Pharmaceutical Sciences Peking Un
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Zhang Q
School Of Pharmaceutical Sciences Peking University
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Zhang Qiang
Department of Hepatology, Capital University of Medical Science Affiliated Beijing You An Hospital
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LU Wan-Liang
Department of Pharmaceutics, Peking University
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Zhang Rui-juan
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University
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QI Xian-Rong
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University
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LI Rong-Yu
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University
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WANG Gui-Lin
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University
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WEI Shu-Li
Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University
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Lu Wan-liang
中華人民共和国
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Zhang Qiang
Department Of Cardiology Beijing Anzhen Hospital Capital Medical University
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Wang Gui-lin
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University
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Li Rong-yu
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University
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Wei Shu-li
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University
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Qi Xian-rong
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University
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Zhang Rui-juan
Department Of Pharmaceutics Peking University School Of Pharmaceutical Sciences
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Wang Gui-lin
Department Of Pharmaceutics Peking University School Of Pharmaceutical Sciences
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Lu Wan-liang
Department Of Pharmaceutics School Of Pharmaceutical Sciences Peking University:state Key Laboratory
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