Document Detail


Proton-actuated membrane-destabilizing polyion complex micelles.
MedLine Citation:
PMID:  17402703     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The efficiency of nucleic acid-based drugs is usually hampered by the fact that, following their uptake by the cell, these drugs end up in acidic organelles (i.e., endosomes/lysosomes) from which they barely escape. This work relates to the preparation and characterization of polyion complex micelles (PICM) formed by the self-assembly of three polyelectrolytes: a diblock cationic copolymer; a membranolytic, methacrylic acid copolymer; and an oligonucleotide. It is demonstrated that a synthetic membrane-active polyanion can be successfully integrated within the structure of PICM to yield well-defined, narrowly distributed micelles (30 nm) with a core/shell architecture. Besides their ability to protect the oligonucleotide against nuclease degradation, PICM partly dissociate under mildly acidic conditions, releasing chain clusters that destabilize bilayer membranes. This association/dissociation behavior illustrates the potential of these pH-sensitive PICM for the transport and efficient delivery of polyionic drugs.
Authors:
Marie-Andrée Yessine; Marie-Hélène Dufresne; Christian Meier; Hans-Ulrich Petereit; Jean-Christophe Leroux
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-04-03
Journal Detail:
Title:  Bioconjugate chemistry     Volume:  18     ISSN:  1043-1802     ISO Abbreviation:  Bioconjug. Chem.     Publication Date:    2007 May-Jun
Date Detail:
Created Date:  2007-05-16     Completed Date:  2007-08-29     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9010319     Medline TA:  Bioconjug Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1010-4     Citation Subset:  IM    
Affiliation:
Canada Research Chair in Drug Delivery, Faculty of Pharmacy, Université de Montréal, C.P. 6128 Succ. Centre-Ville, Montreal, Quebec, H3C 3J7, Canada.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Drug Delivery Systems*
Endosomes / metabolism
Humans
Hydrogen-Ion Concentration
Intracellular Membranes / drug effects,  metabolism
Micelles*
Oligodeoxyribonucleotides / chemistry*,  metabolism
Polymethacrylic Acids / chemistry*,  pharmacology
Protons*
Chemical
Reg. No./Substance:
0/Micelles; 0/Oligodeoxyribonucleotides; 0/Polymethacrylic Acids; 0/Protons

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


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