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.
Kojima
Chie
C
Department of Applied Chemistry, Graduate School of Engineering, Osaka Prefecture University, Osaka, Japan. c-kojima@21c.osakafu-u.ac.jp
Regino
Celeste
C
Umeda
Yasuhito
Y
Kobayashi
Hisataka
H
Kono
Kenji
K
D000818:Animals; D001682:Biological Availability; D050091:Dendrimers / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics; D005260:Female; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008819:Mice, Nude; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000502:physiology
D050091:Dendrimers; D004337:Drug Carriers; C104700:PAMAM Starburst; D011092:Polyethylene Glycols; D008239:Lysine