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Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation

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...

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Autores principales: Sakisaka, Hideto, Takedatsu, Hidetoshi, Mitsuyama, Keiichi, Mochizuki, Shinichi, Sakurai, Kazuo, Sakisaka, Shotaro, Hirai, Fumihito
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014273/
https://www.ncbi.nlm.nih.gov/pubmed/31968666
http://dx.doi.org/10.3390/ijms21020683
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author Sakisaka, Hideto
Takedatsu, Hidetoshi
Mitsuyama, Keiichi
Mochizuki, Shinichi
Sakurai, Kazuo
Sakisaka, Shotaro
Hirai, Fumihito
author_facet Sakisaka, Hideto
Takedatsu, Hidetoshi
Mitsuyama, Keiichi
Mochizuki, Shinichi
Sakurai, Kazuo
Sakisaka, Shotaro
Hirai, Fumihito
author_sort Sakisaka, Hideto
collection PubMed
description 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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spelling pubmed-70142732020-03-09 Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation Sakisaka, Hideto Takedatsu, Hidetoshi Mitsuyama, Keiichi Mochizuki, Shinichi Sakurai, Kazuo Sakisaka, Shotaro Hirai, Fumihito Int J Mol Sci Article 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. MDPI 2020-01-20 /pmc/articles/PMC7014273/ /pubmed/31968666 http://dx.doi.org/10.3390/ijms21020683 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sakisaka, Hideto
Takedatsu, Hidetoshi
Mitsuyama, Keiichi
Mochizuki, Shinichi
Sakurai, Kazuo
Sakisaka, Shotaro
Hirai, Fumihito
Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title_full Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title_fullStr Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title_full_unstemmed Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title_short Topical Therapy with Antisense Tumor Necrosis Factor Alpha Using Novel β-Glucan-Based Drug Delivery System Ameliorates Intestinal Inflammation
title_sort topical therapy with antisense tumor necrosis factor alpha using novel β-glucan-based drug delivery system ameliorates intestinal inflammation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014273/
https://www.ncbi.nlm.nih.gov/pubmed/31968666
http://dx.doi.org/10.3390/ijms21020683
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