Pharmacokinetics and Tissue Distribution of Dual-Targeting Daunorubicin Liposomes in Mice

被引:17
|
作者
Ying, Xue [1 ,2 ,3 ,4 ]
Wen, He [1 ,2 ]
Yao, Hong-Juan [1 ,2 ]
Zhang, Yan [1 ,2 ]
Tian, Wei [1 ,2 ]
Zhang, Liang [1 ,2 ]
Ju, Rui-Jun [1 ,2 ]
Wang, Xiao-Xing [1 ,2 ]
Yu, Yang [1 ,2 ]
Lu, Wan-Liang [1 ,2 ]
机构
[1] Peking Univ, Sch Pharmaceut Sci, Beijing 100191, Peoples R China
[2] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China
[3] Shihezi Univ, Key Lab Phytomed Resources & Modernizat Tradit Ch, Shihezi, Peoples R China
[4] Shihezi Univ, Sch Pharmaceut Sci, Shihezi, Peoples R China
基金
美国国家科学基金会; 北京市自然科学基金;
关键词
Dual-targeting daunorubicin liposomes; Pharmacokinetics; Tissue distribution; HPLC; CLEARANCE ABC PHENOMENON; IN-VIVO; PEGYLATED LIPOSOMES; EFFICACY; DRUG; DERIVATIVES; DOXORUBICIN; MECHANISMS;
D O I
10.1159/000323222
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Background:To circumvent the problem of transporting anticancer drugs across the blood-brain barrier (BBB) to target brain tumors, we have previously developed dual-targeting daunorubicin liposomes modified with 4-aminophenyl-alpha-D-manno-pyranoside and transferrin molecules. The objective of the present study was to evaluate the pharmacokinetics and distribution of daunorubicin after intravenous administration of dual-targeting daunorubicin liposomes. Methods: We evaluated pharmacological parameters in normal Kun-Ming mice. Drug concentrations in plasma, heart, spleen, lung, kidney and brain were measured using HPLC-UV. Results: The plasma drug concentration-time profile of the daunorubicin dual-targeting liposomes decreased more slowly than free daunorubicin in the initial phase and maintained higher drug levels in the terminal phase, resulting in longer blood exposure to daunorubicin liposomes compared with the free drug. Daunorubicin levels were lower in heart tissue and significantly higher in brain tissue after administration of the dual-targeting liposomes compared with the free drug. Daunorubicin was detected at varying levels in the liver, spleen, lung and kidney tissues. Conclusion: Our results indicate that dual-targeting daunorubicin liposomes improve the daunorubicin blood circulation time and show an enhanced drug transport potential across the BBB. Copyright (C) 2011 S. Karger AG, Basel
引用
收藏
页码:105 / 114
页数:10
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