Pharmacokinetics and brain uptake of lactoferrin in rats
Pharmacokinetics and brain uptake of lactoferrin in rats
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DOI：
10.1016/j.lfs.2005.05.085
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发表时间：
2006-01-18
期刊：
影响因子：
6.1
通讯作者：
Suhara, T
中科院分区：
文献类型：
--
作者：
Ji, B;Maeda, A;Suhara, T
乳铁蛋白(LF)是转铁蛋白(Tf)家族中的一种铁结合糖蛋白。据报道，在体外血脑屏障模型中，LF通过受体介导的跨细胞作用穿过血脑屏障(BBB)。在本研究中，我们比较了LF与抗TF受体抗体OX26和TF的体内脑摄取。用125-1标记这三种蛋白，静脉注射给药。注射。我们发现，与OX26和TF相比，LF从血液中的清除速度更快(LF的半衰期分别比OX26和TF短约8倍和6倍；血药浓度-时间曲线下面积分别比OX26和TF小约15倍和17倍)，并主要积累在肝、脾和肾中。与Tf和OX26相比，Lf的脑摄取显著增加。作为一种促进药物进入大脑的配体，IF可能是有用的。(C)2005 Elsevier Inc.保留所有权利。
Lactoferrin (Lf) is an iron-binding glycoprotein belonging to the transferrin (Tf) family. Lf was reported to cross the blood brain barrier (BBB) via receptor-mediated transcytosis in an in vitro model of the BBB. In the present study, we compared the in vivo brain uptake of Lf with that of OX26, an anti-Tf receptor antibody, and Tf. These three proteins were radiolabeled with 125 1 and administered to rats by i.v. injection. We found that Lf was more rapidly eliminated from the blood compared with OX26 and Tf (The half-life of Lf was approximately 8 and 6 times shorter than that of OX26 and Tf, respectively; the area under the blood concentration- time curve of Lf was approximately 15 and 17 times smaller than that of OX26 and Tf, respectively), and mainly accumulated in the liver, spleen, and kidney. Markedly high brain uptake was observed for Lf relative to Tf and OX26. Lf might be useful as a ligand for facilitating drug delivery into the brain. (c) 2005 Elsevier Inc. All rights reserved.