A pegylated liposomal platform: Pharmacokinetics, pharmacodynamics, and toxicity in mice using doxorubicin as a model drug

被引:59
|
作者
Lu, WL [1 ]
Qi, XR [1 ]
Zhang, Q [1 ]
Li, RY [1 ]
Wang, GL [1 ]
Zhang, RJ [1 ]
Wei, SL [1 ]
机构
[1] Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100083, Peoples R China
关键词
pegylated liposomal platform; doxorubicin; pharmacokinetics; pharmacodynamics; toxicity;
D O I
10.1254/jphs.FPJ04001X
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Aims were to observe pharmacokinetics, pharmacodynamics, and toxicity for constructing a Sino-pegylated liposomal platform. Human hepatocarcinoma cells (Bel7402) and murine hepatocarcinoma cells (H-22) 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 (T-1/2,T-gamma) 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 (AUC(0-infinity)) (h(.)mug/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.
引用
收藏
页码:381 / 389
页数:9
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