PEGylated lysine dendrimers for tumor-selective targeting after intravenous injection in tumor-bearing mice.
In this study, we synthesized a sixth generation lysine dendrimer (KG6) and two PEGylated derivatives thereof and evaluated their biodistribution characteristics in both normal and tumor-bearing mice. The intact KG6 showed a rapid clearance from the blood stream and non-specific accumulation in the liver and kidney. In contrast, the PEGylated derivatives showed a better retention in blood and low accumulativeness in organs dependent of the rate of PEGylation. In addition, PEGylated KG6 with a high modification rate was accumulated effectively in tumor tissue via the enhanced permeability and retention (EPR) effect. Moreover, we clarified that multiple administrations did not affect the biodistribution characteristics of a second dose of PEGylated KG6. PEGylated lysine dendrimer would be a useful material for a clinically applicable tumor-targeting carrier.
Okuda
Tatsuya
T
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
Kawakami
Shigeru
S
Akimoto
Naomi
N
Niidome
Takuro
T
Yamashita
Fumiyoshi
F
Hashida
Mitsuru
M
D000818:Animals; D050091:Dendrimers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008239:Lysine / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D013154:Spleen / Q000378:metabolism; D014018:Tissue Distribution
D050091:Dendrimers; D004337:Drug Carriers; D011092:Polyethylene Glycols; D008239:Lysine