Influence of dendrimer generation and polyethylene glycol length on the biodistribution of PEGylated dendrimers

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.