Linked Life Data

20507711

Source:http://linkedlifedata.com/resource/pubmed/id/20507711

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8-9
pubmed:dateCreated
2010-5-28
pubmed:abstractText
The cytotoxicity of polyethylenimine (PEI) was a dominating obstacle to its application. Introduction of poly(ethylene glycol) (PEG) blocks to PEI is one of the strategies to alleviate the cytotoxocity of PEI. However, it is well known that the transfection efficiency of PEGylated PEI is decreased to some extent compared to the corresponding PEI. Thus, the aim of our study was to enhance the transfection efficiency of PEGylated PEI. A series of tri-block co-polymers, PEG-g-PEI-g-poly(dimethylaminoethyl L-glutamine) (PEG-g-PEI-g-PDMAEG), as novel vectors for gene therapy was synthesized and evaluated. PEG-g-PEI was first obtained by linking PEG and PEI using isophorone diisocyanate (IPDI) as coupling reagent. The anionic co-polymerization of gamma-benzyl-L-glutamate N-carboxyanhydride (BLG-NCA) using PEG-g-PEI as a macro-initiator was carried out, followed by aminolysis with 2-dimethylaminoethylamine to obtain the target water-soluble tri-block co-polymer. The structures of the polymers were confirmed by FT-IR and (1)H-NMR. The influence of the molecular weight of PEI and the length of the PDMAEG chain on the physicochemical properties and transfection activity of polymer/DNA was evaluated. All PEI derivates were revealed to compact plasmid DNA effectively to give polyplexes with suitable size (approx. 100 nm) and moderate zeta potentials (10-15 mV) at N/P ratios over 10. The PEG-g-PEI-g-PDMAEG tri-block co-polymers displayed particularly low cytotoxicity, even at high concentration, reflecting an improved safety profile compared to PEI 25k. Gene transfection efficiency of PEG-g-PEI-g-PDMAEG on HeLa in the presence and absence of serum was determined. Remarkably, the transfection activity of PEG-g-PEI (10k)-g-PDMAEG (PPP-4)/DNA polyplex formulations was nearly twofold higher than PEI 25k/DNA formulations in vitro, and the transfection efficiency was less affected by the presence of serum. These results indicated that the synthesized PEG-g-PEI-g-PDMAEG tri-block co-polymers are promising candidates as carriers for gene delivery.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1568-5624
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
21
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1103-26
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:20507711-Biocompatible Materials, pubmed-meshheading:20507711-Buffers, pubmed-meshheading:20507711-Colloids, pubmed-meshheading:20507711-DNA, pubmed-meshheading:20507711-Electrophoretic Mobility Shift Assay, pubmed-meshheading:20507711-Glutamates, pubmed-meshheading:20507711-HeLa Cells, pubmed-meshheading:20507711-Humans, pubmed-meshheading:20507711-Hydrophobic and Hydrophilic Interactions, pubmed-meshheading:20507711-Light, pubmed-meshheading:20507711-Molecular Weight, pubmed-meshheading:20507711-Particle Size, pubmed-meshheading:20507711-Peptides, pubmed-meshheading:20507711-Polyethylene Glycols, pubmed-meshheading:20507711-Polyethyleneimine, pubmed-meshheading:20507711-Scattering, Radiation, pubmed-meshheading:20507711-Spectrum Analysis, pubmed-meshheading:20507711-Transfection
pubmed:year
2010
pubmed:articleTitle
PEG- and PDMAEG-graft-modified branched PEI as novel gene vector: synthesis, characterization and gene transfection.
pubmed:affiliation
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510080, P. R. China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't