An orally administrated nucleotide-delivery vehicle targeting colonic macrophages for the treatment of inflammatory bowel disease.

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.

• Authors: Zhen Huang, Jingjing Gan, Lixin Jia, Guangxing Guo, Chunming Wang, Yuhui Zang, Zhi Ding, Jiangning Chen, Junfeng Zhang, Lei Dong
• Journal: Biomaterials (Biomaterials) Vol. 48 Pg. 26-36 (Apr 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25701029 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Nucleotides
• Tumor Necrosis Factor-alpha

Topics

• Administration, Oral
• Animals
• Cell Line
• Colon (drug effects, metabolism, pathology)
• In Vitro Techniques
• Inflammatory Bowel Diseases (drug therapy)
• Macrophages (drug effects)
• Mice
• Microscopy, Electron, Transmission
• Microspheres
• Nucleotides (administration & dosage, pharmacokinetics)
• Spectroscopy, Fourier Transform Infrared
• Tissue Distribution
• Tumor Necrosis Factor-alpha (biosynthesis)