Document Detail


An acid-labile block copolymer of PDMAEMA and PEG as potential carrier for intelligent gene delivery systems.
MedLine Citation:
PMID:  18088093     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Intelligent gene delivery systems based on physiologically triggered reversible shielding technology have evinced enormous interest due to their potential in vivo applications. In the present work, an acid-labile block copolymer consisting of poly(ethylene glycol) and poly(2-(dimethylamino)ethyl methacrylate) segments connected through a cyclic ortho ester linkage (PEG- a-PDMAEMA) was synthesized by atom transfer radical polymerization of DMAEMA using a PEG macroinitiator with an acid-cleavable end group. PEG- a-PDMAEMA condensed with plasmid DNA formed polyplex nanoparticles with an acid-triggered reversible PEG shield. The pH-dependent shielding/deshielding effect of PEG chains on the polyplex particles were evaluated by zeta potential and size measurements. At pH 7.4, polyplexes generated from PEG- a-PDMAEMA exhibited smaller particle size, lower surface charge, reduced interaction with erythrocytes, and less cytotoxicity compared to PDMAEMA-derived polyplexes. At pH 5.0, zeta potential of polyplexes formed from PEG- a-PDMAEMA increased, leveled up after 2 h of incubation and gradual aggregation occurred in the presence of bovine serum albumin (BSA). In contrast, the stably shielded polyplexes formed by DNA and an acid-stable block copolymer, PEG- b-PDMAEMA, did not change in size and zeta potential in 6 h. In vitro transfection efficiency of the acid-labile copolymer greatly increased after 6 h incubation at pH 5.0, approaching the same level of PDMAEMA, whereas there was only slight increase in efficiency for the stable copolymer, PEG- b-PDMAEMA.
Authors:
Song Lin; Fusheng Du; Yang Wang; Shouping Ji; Dehai Liang; Lei Yu; Zichen Li
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Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-19
Journal Detail:
Title:  Biomacromolecules     Volume:  9     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2008-01-14     Completed Date:  2008-03-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  United States    
Other Details:
Languages:  eng     Pagination:  109-15     Citation Subset:  IM    
Affiliation:
Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry & Molecular Engineering, Peking University, Beijing 100871, PR China.
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MeSH Terms
Descriptor/Qualifier:
Acids / chemistry*
Drug Carriers
Electrophoresis, Agar Gel
Erythrocytes / drug effects
Hemolysis
Humans
Hydrogen-Ion Concentration
Methacrylates / chemistry*,  pharmacology
Nylons / chemistry*,  pharmacology
Particle Size
Polyethylene Glycols / chemistry*,  pharmacology
Transfection*
Chemical
Reg. No./Substance:
0/Acids; 0/Drug Carriers; 0/Methacrylates; 0/Nylons; 0/Polyethylene Glycols; 0/poly(2-(dimethylamino)ethyl methacrylate)

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