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pubmed-article:20970849pubmed:abstractTextDuring 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.lld:pubmed
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pubmed-article:20970849pubmed:issn1878-5905lld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:MerlinDidierDlld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:SitaramanShan...lld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:DalmassoGuill...lld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:YanYutaoYlld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:TheissArianne...lld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:LarouiHamedHlld:pubmed
pubmed-article:20970849pubmed:authorpubmed-author:NguyenHang...lld:pubmed
pubmed-article:20970849pubmed:copyrightInfoCopyright © 2010 Elsevier Ltd. All rights reserved.lld:pubmed
pubmed-article:20970849pubmed:issnTypeElectroniclld:pubmed
pubmed-article:20970849pubmed:volume32lld:pubmed
pubmed-article:20970849pubmed:ownerNLMlld:pubmed
pubmed-article:20970849pubmed:authorsCompleteYlld:pubmed
pubmed-article:20970849pubmed:pagination1218-28lld:pubmed
pubmed-article:20970849pubmed:dateRevised2011-4-21lld:pubmed
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pubmed-article:20970849pubmed:year2011lld:pubmed
pubmed-article:20970849pubmed:articleTitleFunctional TNF? gene silencing mediated by polyethyleneimine/TNF? siRNA nanocomplexes in inflamed colon.lld:pubmed
pubmed-article:20970849pubmed:affiliationDepartment of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA, United States. hlaroui@emory.edulld:pubmed
pubmed-article:20970849pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:20970849pubmed:publicationTypeResearch Support, U.S. Gov't, Non-P.H.S.lld:pubmed
pubmed-article:20970849pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
pubmed-article:20970849pubmed:publicationTypeEvaluation Studieslld:pubmed
pubmed-article:20970849pubmed:publicationTypeResearch Support, N.I.H., Extramurallld:pubmed