Document Detail


PEGylated dendrimers with core functionality for biological applications.
MedLine Citation:
PMID:  18173227     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The synthesis of a variety of core functionalized PEGylated polyester dendrimers and their in vitro and in vivo properties are described in this report. These water-soluble dendrimers have been designed to carry eight functional groups on their dendritic core for a variety of biological applications such as drug delivery and in vivo imaging as well as eight solubilizing groups. Using a common symmetrical aliphatic ester dendritic core and trifunctional amino acid moieties, a library of dendrimers with phenols, alkyl alcohols, alkynes, ketones, and carboxylic acid functionalities has been synthesized without the need for column chromatography. The amines were PEGylated, leaving the other functionality of the amino acid available for further manipulation such as the attachment of drugs and/or labels. Radiolabeling experiments with the PEGylated dendrimers showed that they had a long circulation half-life in mice, confirming the potential of this class of dendrimers for therapeutic and/or diagnostic applications. A carboxylic acid functionalized dendrimer was elaborated to carry doxorubicin bound via a hydrazone bond. The drug-loaded carrier accumulated more in tumors and less in healthy organs than the clinically used PEGylated liposomal formulation Doxil. The efficient synthesis, high versatility, and favorable biological properties make these PEGylated polyester dendrimers promising structures for therapeutic and/or imaging applications.
Authors:
Steven J Guillaudeu; Megan E Fox; Yarah M Haidar; Edward E Dy; Francis C Szoka; Jean M J Fréchet
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2008-01-04
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  19     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-21     Completed Date:  2008-05-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  461-9     Citation Subset:  IM    
Affiliation:
College of Chemistry, University of California, Berkeley, California 94720-1460, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Dendrimers / chemistry*,  pharmacokinetics
Magnetic Resonance Spectroscopy
Mice
Polyethylene Glycols / chemistry*,  pharmacokinetics
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tissue Distribution
Grant Support
ID/Acronym/Agency:
EB 002047/EB/NIBIB NIH HHS; GM 65361/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Dendrimers; 0/Polyethylene Glycols

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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