| Functional TNFα gene silencing mediated by polyethyleneimine/TNFα siRNA nanocomplexes in inflamed colon. | |
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MedLine Citation:
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PMID: 20970849 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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During inflammatory bowel disease, TNFα is the major pro-inflammatory cytokine mainly secreted from macrophages and dendritic cells. Here, we have demonstrated that TNFα 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 TNFα 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 TNFα siRNA and polyethyleneimine were higher than those using chitosan. Importantly, complexation between TNFα siRNA and polyethyleneimine facilitated higher rates of siRNA loading into nanoparticles, compared to Chi or free siRNA mixed with Lipofectamine. Oral administration of encapsulated TNFα siRNA-loaded nanoparticles specifically reduced the TNFα expression/secretion in colonic tissue in LPS-treated mice. In conclusion, we have shown: (1) that proposed TNFα siRNA-loaded NPs are prepared via a non-denaturing synthetic process; (2) a high encapsulation rate of TNFα siRNA complexed to polyethyleneimine into NPs; (3) effective enzymatic protection of TNFα siRNA by polyethyleneimine; (4) non-cytotoxicity and biodegradability of nanoparticles loaded with polyethyleneimine/TNFα siRNA; and (5) in vitro and in vivo significant anti-inflammatory effects at low TNFα siRNA dose that is specific and restricted to the colonic cells. Our results collectively indicate that polyethyleneimine/TNFα siRNA nanocomplexes represent an efficient therapeutic option for diseases such as IBD. |
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Authors:
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Hamed Laroui; Arianne L Theiss; Yutao Yan; Guillaume Dalmasso; Hang T T Nguyen; Shanthi V Sitaraman; Didier Merlin |
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Publication Detail:
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Type: Evaluation Studies; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S. |
Journal Detail:
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Title: Biomaterials Volume: 32 ISSN: 1878-5905 ISO Abbreviation: Biomaterials Publication Date: 2011 Feb |
Date Detail:
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Created Date: 2010-11-26 Completed Date: 2011-03-04 Revised Date: 2012-02-02 |
Medline Journal Info:
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Nlm Unique ID: 8100316 Medline TA: Biomaterials Country: England |
Other Details:
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Languages: eng Pagination: 1218-28 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Ltd. All rights reserved. |
Affiliation:
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Department of Medicine, Division of Digestive Diseases, Emory University, Atlanta, GA, United States. hlaroui@emory.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Colon / metabolism*, pathology* Gene Silencing* Humans Inflammatory Bowel Diseases / metabolism, pathology, therapy Macrophages / metabolism Materials Testing Mice Nanoparticles / chemistry*, therapeutic use Polyethyleneimine / chemistry*, metabolism RNA, Small Interfering / chemistry, genetics, metabolism* Tumor Necrosis Factor-alpha / genetics*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K01 DK085222-04/DK/NIDDK NIH HHS; K01-DK085222/DK/NIDDK NIH HHS; R01 DK071594-06/DK/NIDDK NIH HHS; R01-DK-071594/DK/NIDDK NIH HHS; R01-DK55850/DK/NIDDK NIH HHS; R24-DK-064399/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/RNA, Small Interfering; 0/Tumor Necrosis Factor-alpha; 9002-98-6/Polyethyleneimine |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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