A pegylated liposomal platform: Pharmacokinetics, pharmacodynamics, and toxicity in mice using doxorubicin as a model drug
A pegylated liposomal platform: Pharmacokinetics, pharmacodynamics, and toxicity in mice using doxorubicin as a model drug
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DOI：
10.1254/jphs.fpj04001x
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Wei, SL
中科院分区：
文献类型：
--
作者：
Lu, WL;Qi, XR;Wei, SL
目的是观察构建中国聚乙二醇化脂质体平台的药代动力学、药效学和毒性。人肝癌细胞（Bel7402）和鼠肝癌细胞（H-22）分别用于细胞毒性测定和小鼠体内实体异种移植肿瘤模型。小鼠药代动力学结果表明，聚乙二醇化阿霉素脂质体可显着延长阿霉素的血液循环。聚乙二醇化、常规脂质体阿霉素和游离阿霉素的消除半衰期（T-1/2，T-gamma）分别为46.09+/-14.44、26.04+/-3.34和23.72+/-5.13小时。聚乙二醇化和普通脂质体阿霉素的浓度-时间曲线下面积(AUC(0-无穷大)) (h(.)mug/g)分别比游离阿霉素高6.8倍和2.6倍。体内细胞毒性和抗肿瘤活性表明，聚乙二醇化脂质体阿霉素的活性分别高于常规脂质体和游离脂质体。单剂量10 mg/kg尾静脉注射聚乙二醇化脂质体阿霉素两周后，胃、肠粘膜和心肌未观察到明显损伤，但给予游离阿霉素后对照组出现明显损伤。结果表明，聚乙二醇化脂质体提高了毒物的药效，降低了毒性，为构建聚乙二醇化脂质体平台提供了有利的证据。
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.