Linked Life Data

20970849

Source:http://linkedlifedata.com/resource/pubmed/id/20970849

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2010-11-26
pubmed:abstractText
During inflammatory bowel disease, TNF? is the major pro-inflammatory cytokine mainly secreted from macrophages and dendritic cells. Here, we have demonstrated that TNF? siRNA/polyethyleneimine loaded into polylactide at an optimal concentration of 20 g/L nanoparticles covered with polyvinyl alcohol are efficiently taken up by inflamed macrophages and inhibit TNF? secretion by the macrophages. Those nanoparticles have a diameter of ?380 nm and zeta potential of -8 mV at pH 7.2, and are non-cytotoxic. Complexation, interactions and protection from RNAse between TNF? siRNA and polyethyleneimine were higher than those using chitosan. Importantly, complexation between TNF? siRNA and polyethyleneimine facilitated higher rates of siRNA loading into nanoparticles, compared to Chi or free siRNA mixed with Lipofectamine. Oral administration of encapsulated TNF? siRNA-loaded nanoparticles specifically reduced the TNF? expression/secretion in colonic tissue in LPS-treated mice. In conclusion, we have shown: (1) that proposed TNF? siRNA-loaded NPs are prepared via a non-denaturing synthetic process; (2) a high encapsulation rate of TNF? siRNA complexed to polyethyleneimine into NPs; (3) effective enzymatic protection of TNF? siRNA by polyethyleneimine; (4) non-cytotoxicity and biodegradability of nanoparticles loaded with polyethyleneimine/TNF? siRNA; and (5) in vitro and in vivo significant anti-inflammatory effects at low TNF? siRNA dose that is specific and restricted to the colonic cells. Our results collectively indicate that polyethyleneimine/TNF? siRNA nanocomplexes represent an efficient therapeutic option for diseases such as IBD.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1878-5905
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier Ltd. All rights reserved.
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1218-28
pubmed:dateRevised
2011-4-21
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Functional TNF? gene silencing mediated by polyethyleneimine/TNF? siRNA nanocomplexes in inflamed colon.
pubmed:affiliation
Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA, United States. hlaroui@emory.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't, Evaluation Studies, Research Support, N.I.H., Extramural