Document Detail


Biodistribution characteristics of amino acid dendrimers and their PEGylated derivatives after intravenous administration.
MedLine Citation:
PMID:  16814896     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In this study, we synthesized dendritic poly(L-lysine)s (DPKs), dendritic poly(L-ornithine)s (DPOs), which are constructed as novel amino acid dendrimers, and PEGylated KG6 (the sixth generation of DPKs), and evaluated the physicochemical properties and biodistribution characteristics of these dendrimers. The particle size of DPKs and DPOs was well controlled in the nanometer range. The zeta-potential of these dendrimers was slightly positive and this gradually increased in association with their generation. After intravenous administration to mice, all tested dendrimers cleared rapidly from blood flow and mainly accumulated in the liver and kidney. The hepatic and renal accumulation changed in a generation-dependent manner. In contrast, no significant distributional differences between same generation of DPK and DPO were observed, although the constituent amino acids, particle size, and zeta-potential were different. However, PEGylation of KG6 caused great changes in particle size, zeta-potential, blood retention and organ distribution in vivo, indicating that the PEGylation is applicable strategy to improve biodistribution characteristics of dendrimeric molecules. The information provided by this study will be helpful for the development of future drug delivery systems using amino acid dendrimers as safe drug carriers.
Authors:
Tatsuya Okuda; Shigeru Kawakami; Tadahiro Maeie; Takuro Niidome; Fumiyoshi Yamashita; Mitsuru Hashida
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-05-23
Journal Detail:
Title:  Journal of controlled release : official journal of the Controlled Release Society     Volume:  114     ISSN:  0168-3659     ISO Abbreviation:  J Control Release     Publication Date:  2006 Aug 
Date Detail:
Created Date:  2006-08-04     Completed Date:  2006-09-26     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8607908     Medline TA:  J Control Release     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  69-77     Citation Subset:  IM    
Affiliation:
Department of Drug Delivery Research, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-Shimo-Adachi-cho, Sakyo-ku, Kyoto 606-8501, Japan.
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MeSH Terms
Descriptor/Qualifier:
Alanine Transaminase / blood
Amino Acids / chemistry*
Animals
Dendrimers / administration & dosage,  chemistry,  pharmacokinetics*
Injections, Intravenous
Male
Mice
Mice, Inbred Strains
Molecular Weight
Particle Size
Peptides / chemical synthesis,  chemistry
Polyethylene Glycols / chemistry*
Polylysine / chemical synthesis,  chemistry
Static Electricity
Surface Properties
Tissue Distribution
Chemical
Reg. No./Substance:
0/Amino Acids; 0/Dendrimers; 0/Peptides; 0/Polyethylene Glycols; 25104-12-5/polyornithine; 25104-18-1/Polylysine; EC 2.6.1.2/Alanine Transaminase

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