Cargando…
Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis
Chitosan is used in various drug delivery approaches as a pharmaceutical excipient. Although its potential as an immunomodulatory agent has been reported, its use in this capacity has not been fully explored. The efficacy of chitosan as an active pharmacological agent, particularly in anti-inflammat...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692366/ https://www.ncbi.nlm.nih.gov/pubmed/33138176 http://dx.doi.org/10.3390/pharmaceutics12111038 |
_version_ | 1783614494331633664 |
---|---|
author | Jhundoo, Henusha D. Siefen, Tobias Liang, Alfred Schmidt, Christoph Lokhnauth, John Béduneau, Arnaud Pellequer, Yann Larsen, Crilles Casper Lamprecht, Alf |
author_facet | Jhundoo, Henusha D. Siefen, Tobias Liang, Alfred Schmidt, Christoph Lokhnauth, John Béduneau, Arnaud Pellequer, Yann Larsen, Crilles Casper Lamprecht, Alf |
author_sort | Jhundoo, Henusha D. |
collection | PubMed |
description | Chitosan is used in various drug delivery approaches as a pharmaceutical excipient. Although its potential as an immunomodulatory agent has been reported, its use in this capacity has not been fully explored. The efficacy of chitosan as an active pharmacological agent, particularly in anti-inflammatory therapy in inflammatory bowel diseases (IBD), was investigated in this study. The potential impact of the molecular weight (MW) and degree of deacetylation (DD) of chitosan was investigated together with 5-amino salicylic acid (5-ASA) for its efficacy in a combination anti-inflammatory therapy in murine experimental colitis. Such a combination would potentially be developed into novel dual strategies whereby chitosan acts as a mucoadhesive excipient as well as provide an additional anti-inflammatory benefit. Chitosan grades with different MW and DD were administered intrarectally alone or in combination with 5-ASA to colitis mice for 3 days. Myeloperoxidase (MPO) and alkaline phosphatase (ALP) activity and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor kappa-B (NF-κB) levels were assessed from the colon. Intrarectal treatment of colitis with 30 mg/kg chitosan alone and with 30 mg/kg 5-ASA for 3 days led to a significant decrease in MPO, ALP, TNF-α, IL-6, IL-1β and NF-κB in colitis mice compared to untreated mice. Surprisingly, the efficacy of chitosan as an anti-inflammatory polymer was relatively independent from its structural properties, namely DD and MW. However, combinations of chitosan with 5-ASA showed a significant pharmacological improvement, whereby the additive anti-inflammatory efficacy observed shows the possibility of finetuning chitosan by combining it with anti-inflammatory agents to optimize its anti-inflammatory potential. |
format | Online Article Text |
id | pubmed-7692366 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76923662020-11-28 Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis Jhundoo, Henusha D. Siefen, Tobias Liang, Alfred Schmidt, Christoph Lokhnauth, John Béduneau, Arnaud Pellequer, Yann Larsen, Crilles Casper Lamprecht, Alf Pharmaceutics Article Chitosan is used in various drug delivery approaches as a pharmaceutical excipient. Although its potential as an immunomodulatory agent has been reported, its use in this capacity has not been fully explored. The efficacy of chitosan as an active pharmacological agent, particularly in anti-inflammatory therapy in inflammatory bowel diseases (IBD), was investigated in this study. The potential impact of the molecular weight (MW) and degree of deacetylation (DD) of chitosan was investigated together with 5-amino salicylic acid (5-ASA) for its efficacy in a combination anti-inflammatory therapy in murine experimental colitis. Such a combination would potentially be developed into novel dual strategies whereby chitosan acts as a mucoadhesive excipient as well as provide an additional anti-inflammatory benefit. Chitosan grades with different MW and DD were administered intrarectally alone or in combination with 5-ASA to colitis mice for 3 days. Myeloperoxidase (MPO) and alkaline phosphatase (ALP) activity and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and nuclear factor kappa-B (NF-κB) levels were assessed from the colon. Intrarectal treatment of colitis with 30 mg/kg chitosan alone and with 30 mg/kg 5-ASA for 3 days led to a significant decrease in MPO, ALP, TNF-α, IL-6, IL-1β and NF-κB in colitis mice compared to untreated mice. Surprisingly, the efficacy of chitosan as an anti-inflammatory polymer was relatively independent from its structural properties, namely DD and MW. However, combinations of chitosan with 5-ASA showed a significant pharmacological improvement, whereby the additive anti-inflammatory efficacy observed shows the possibility of finetuning chitosan by combining it with anti-inflammatory agents to optimize its anti-inflammatory potential. MDPI 2020-10-29 /pmc/articles/PMC7692366/ /pubmed/33138176 http://dx.doi.org/10.3390/pharmaceutics12111038 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 Jhundoo, Henusha D. Siefen, Tobias Liang, Alfred Schmidt, Christoph Lokhnauth, John Béduneau, Arnaud Pellequer, Yann Larsen, Crilles Casper Lamprecht, Alf Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title | Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title_full | Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title_fullStr | Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title_full_unstemmed | Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title_short | Anti-Inflammatory Activity of Chitosan and 5-Amino Salicylic Acid Combinations in Experimental Colitis |
title_sort | anti-inflammatory activity of chitosan and 5-amino salicylic acid combinations in experimental colitis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7692366/ https://www.ncbi.nlm.nih.gov/pubmed/33138176 http://dx.doi.org/10.3390/pharmaceutics12111038 |
work_keys_str_mv | AT jhundoohenushad antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT siefentobias antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT liangalfred antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT schmidtchristoph antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT lokhnauthjohn antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT beduneauarnaud antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT pellequeryann antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT larsencrillescasper antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis AT lamprechtalf antiinflammatoryactivityofchitosanand5aminosalicylicacidcombinationsinexperimentalcolitis |