Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan.
Int J Pharm. 2010 Jan 4;383(1-2):293-6. doi: 10.1016/j.ijpharm.2009.09.015. Epub 2009 Sep 15.
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.
树枝状聚合物是一种有潜力的药物载体。由于聚乙二醇（PEG）的修饰已知可以提高血液保留率，因此 PEG 化树枝状聚合物已被研究作为有用的药物载体。在这项研究中，合成了三种类型的带聚赖氨酸的聚酰胺胺树枝状聚合物（PEG2k-Lys-PAMAM（G4）、PEG5k-Lys-PAMAM（G4）、PEG2k-Lys-PAMAM（G5）），它们由不同代（第 4 代和第 5 代）的树枝状聚合物和不同分子量（2k 和 5k）的 PEG 链组成。还合成了一种带乙酰化赖氨酸的非 PEG 化树枝状聚合物。双功能二亚乙基三胺五乙酸（pSCN-苄基-DTPA）与树枝状聚合物中赖氨酸的ε-氨基结合，以便用放射性铟-111 标记。与非 PEG 化树枝状聚合物相比，这些 PEG 化树枝状聚合物在血液中的保留时间更长，在肾脏等其他正常器官中的积累量更低。具有较高代和较长 PEG 的 PEG 化树枝状聚合物导致更大的血液保留。
