Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo
Factors governing the in vivo tissue uptake of transferrin-coupled polyethylene glycol liposomes in vivo
复制标题
DOI：
10.1016/j.ijpharm.2004.05.025
复制
发表时间：
2004-08-20
影响因子：
5.8
通讯作者：
Harashima, H
中科院分区：
文献类型：
--
作者：
Hatakeyama, H;Akita, H;Harashima, H
涂有转铁蛋白（Tf）偶联聚乙二醇的脂质体被认为是通过受体介导的内吞作用将药物递送至各种器官的有效载体。由于 Tf 受体在各种器官中普遍表达，因此可能需要对脂质体进行额外的扰动，例如调节大小，以表现出组织选择性。在本研究中，研究了尺寸对转铁蛋白偶联聚乙二醇脂质体（Tf-PEG-L）被各种器官摄取的影响。在肝脏和大脑中，Tf 依赖性吸收被发现取决于所用脂质体的大小。在直径为 60-80 nm 的小脂质体中，Tf-PEG-L 比 PEG-L 更有效地被这些器官吸收。这种小脂质体的 Tf 依赖性摄取因高剂量给药而减少，表明即使在内源性 Tf 血浆浓度保持较高的生理条件下，Tf-PEG-L 也通过 Tf 受体介导的内吞作用被脂质体摄取。另一方面，在心脏中也观察到 Tf 受体介导的摄取，但在这种情况下没有观察到大小依赖性。总的来说，这些结果表明 Tf-PEG-L 摄取的大小依赖性是组织依赖性的，因此，控制 Tf-PEG-L 的大小可能有助于组织靶向的成功。 (C) 2004 Elsevier B.V. 保留所有权利。
Liposomes, coated with transferrin (Tf)-coupled polyethylene glycol are considered to be potent carriers for drug delivery to various organs via receptor-mediated endocytosis. Since Tf receptors were ubiquitously expressed in various organs, additional perturbation of the liposomes such as regulation of the size may be required to exhibit the tissue selectivity. In the present study, the effect of size on the uptake of transferrin-coupled polyethylene glycol liposomes (Tf-PEG-L) to various organs was investigated. In liver and brain, Tf-dependent uptake was found to be dependent on the size of the liposomes used. In small liposomes with a diameter of 60-80 nm, Tf-PEG-L was taken up to these organs more efficiently than PEG-L. This Tf-dependent uptake for small liposomes decreased by the high dose administration, suggested that Tf-PEG-L is taken Lip via Tf receptor-mediated endocytosis even under the physiological condition, in which plasma concentration of endogenous Tf remains high. On the other hand, Tf receptor-mediated uptake was also observed in the heart, but size-dependency was not observed in this case. Collectively, these results indicate that size dependency in the uptake of Tf-PEG-L is tissue-dependent and therefore, controlling the size of Tf-PEG-L may be useful for the Success of tissue targeting. (C) 2004 Elsevier B.V. All rights reserved.