Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers
Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers
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DOI：
10.1016/j.ijpharm.2009.09.015
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发表时间：
2010-01-04
影响因子：
5.8
通讯作者：
Kono, Kenji
中科院分区：
文献类型：
--
作者：
Kojima, Chie;Regino, Celeste;Kono, Kenji
树枝状大分子是一种潜在的药物载体。由于已知用聚乙二醇（PEG）修饰可以改善血液保留，因此已经研究了PEG化树状聚合物作为有用的药物载体。本研究合成了三种含聚乙二醇化赖氨酸的聚酰胺-胺树枝状大分子（PEG 2k-Lys-PAMAM（G4）、PEG 5 k-Lys-PAMAM（G4）、PEG 2k-Lys-PAMAM（G5）），它们由不同代数（第4代和第5代）的树枝状大分子和不同分子量（2k和5 k）的PEG链组成。乙酰化的L-赖氨酸承载的树枝状聚合物也被合成为非PEG化的树枝状聚合物。将双官能二亚乙基三胺五乙酸（PSCN-苄基-DTPA）与树枝状大分子中赖氨酸的N-氨基结合，用放射性铟-111标记。这些PEG化的树枝状聚合物显示出比非PEG化的树枝状聚合物更长的血液滞留和更低的在其他正常器官如肾脏中的积累。具有较高代次和较长PEG的PEG化树枝状大分子导致更大的血液滞留。(C)2009 Elsevier B. V.保留所有权利。
Dendrimers are a potential drug carrier. Because modification with polyethylene glycol (PEG) is known to improve the blood retention, PEGylated dendrimers have been studied as a useful drug carrier. In this study, three types of PEGylated L-lysine-bearing polyamidoamine dendrimers (PEG2k-Lys-PAMAM (G4), PEG5k-Lys-PAMAM (G4), PEG2k-Lys-PAMAM (G5)) were synthesized, which are composed of a dendrimer of different generations (generations 4 and 5)and PEG chains with different molecular weights (2k and 5k). An acetylated L-lysine-bearing dendrimer was also synthesized as a non-PEGylated dendrimer. Bifunctional diethylenetriaminepentaacetic acid (PSCN-benzyl-DTPA) was bound to the epsilon -amino group of lysine in a dendrimer, to be labeled with radioactive indium-111. These PEGylayed dendrimers showed longer blood retention and lower accumulation in other normal organs such as the kidneys than the non-PEGylated dendrimer. The PEGylated dendrimers with the higher generation and the longer PEG led the greater blood retention. (C) 2009 Elsevier B.V. All rights reserved.