Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation.
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| Abstract |
Anti-tumor necrosis factor alpha (TNF-α) antibodies are effective in patients with inflammatory bowel disease (IBD). However, the effect is not optimal because a sufficient concentration of antibodies cannot be maintained at the site of inflammation. Thus, a macromolecular complex was developed with schizophyllan (SPG) and antisense oligonucleotides. In the present study, an SPG-antisense TNF-α complex was prepared, and its therapeutic efficacy was examined using a dextran sodium sulfate (DSS)-induced colitis model. The TNF-α production in CD11b+ macrophages significantly increased in the colon of DSS-treated mice. Dectin-1, a receptor of SPG, binds with SPG and is subsequently taken into the cells via phagocytosis. The expression of dectin-1 by CD11b+ macrophages significantly increased in DSS-treated mice. Flow cytometry revealed that the uptake of SPG-antisense TNF-α in the macrophages was efficient. TNF-α production was suppressed significantly by SPG-antisense TNF-α in vitro, which was administered via enema to evaluate its efficacy. The intrarectal administration of SPG-antisense TNF-α ameliorated the intestinal inflammation. In this study, we showed that the delivery system that conjugates SPG and antisense can have higher therapeutic efficacy. Thus, the new therapeutic approach presented in this study may be used in the management of IBD.
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| Authors | Hideto Sakisaka, Hidetoshi Takedatsu, Keiichi Mitsuyama, Shinichi Mochizuki, Kazuo Sakurai, Shotaro Sakisaka, Fumihito Hirai |
| Journal | International journal of molecular sciences (Int J Mol Sci) Vol. 21 Issue 2 (Jan 20 2020) ISSN: 1422-0067 [Electronic] Switzerland |
| PMID | 31968666 (Publication Type: Journal Article) |
| Chemical References |
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