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An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease
Huang Z.1; Gan J.1; Jia L.1; Guo G.1; Wang C.1,2; Zang Y.1; Ding Z.1; Chen J.1; Zhang J.3; Dong L.3
2015
Source PublicationBiomaterials
ISSN1429612
Volume48Pages:26
Abstract

Tumor necrosis factor-alpha (TNF-α) plays a central role in the pathogenesis of inflammatory bowel disease (IBD). Anti-TNF-α therapies have shown protective effects against colitis, but an efficient tool for target suppression of its secretion - ideally via oral administration - remains in urgent demand. In the colon tissue, TNF-α is mainly secreted by the colonic macrophages. Here, we report an orally-administrated microspheric vehicle that can target the colonic macrophages and suppress the local expression of TNF-α for IBD treatment. This vehicle is formed by cationic konjac glucomannan (cKGM), phytagel and an antisense oligonucleotide against TNF-α. It was given to dextran sodium sulfate (DSS) colitic mice via gastric perfusion. The unique swelling properties of cKGM enabled the spontaneous release of cKGM& antisense nucleotide (ASO) nano-complex from the phytagel scaffold into the colon lumen, where the ASO was transferred into colonic macrophages via receptor-mediated phagocytosis. The treatment significantly decreased the local level of TNF-α and alleviated the symptoms of colitis in the mice. In summary, our study demonstrates a convenient, orally-administrated drug delivery system that effectively targets colonic macrophages for suppression of TNF-α expression. It may represent a promising therapeutic approach in the treatment of IBD. © 2015 Elsevier Ltd.

KeywordAntisense Oligonucleotide Colonic Macrophages Inflammatory Bowel Disease Targeting Delivery Tnf-α
DOI10.1016/j.biomaterials.2015.01.013
URLView the original
Language英语
WOS Research AreaEngineering ; Materials Science
WOS SubjectEngineering, Biomedical ; Materials Science, bioMaterials
WOS IDWOS:000350928600003
The Source to ArticleScopus
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Cited Times [WOS]:27   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorZhang J.; Dong L.
Affiliation1.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
2.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau SAR, Macau 999078, China
3.State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, China
Recommended Citation
GB/T 7714
Huang Z.,Gan J.,Jia L.,et al. An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease[J]. Biomaterials,2015,48:26.
APA Huang Z..,Gan J..,Jia L..,Guo G..,Wang C..,...&Dong L..(2015).An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease.Biomaterials,48,26.
MLA Huang Z.,et al."An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease".Biomaterials 48(2015):26.
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