Abstract
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.
Highlights
Inflammatory bowel disease (IBD) is characterized by recurrent episodes of inflammation in the gastrointestinal tract (GIT) with periods of remission and symptoms such as abdominal pain, diarrhoea, rectal bleeding and weight loss
It has been suggested that the biological activities of chitosan may depend on the molecular weight (MW) and the degree of deacetylation (DD) of the parent chitosan material and these properties are inherently affected by the distribution pattern of d- glucosamine (GlcN) and β-1,4-linked N-acetyl-d-glucosamine (GlcNAc) along the oligomeric chain of the parent chitosan [26,27,28,29]
Since no systematic study has been conducted to date to investigate the effect of MW and DD of chitosan in IBD, our study helps to get a better insight into the impact of these molecular properties
Summary
Inflammatory bowel disease (IBD) is characterized by recurrent episodes of inflammation in the gastrointestinal tract (GIT) with periods of remission and symptoms such as abdominal pain, diarrhoea, rectal bleeding and weight loss. While most approaches focus on the design of delivery systems that release the drug to the site of inflamed tissue by selecting excipients to optimize the delivery, the potential anti-inflammatory effect of excipients as single agents or in combination with other drugs has been hardly analyzed to date. This could be of major benefit in therapy since the known active pharmaceutical ingredient could be complemented by an excipient that fulfils formulation-related functions and provides a direct therapeutic effect itself. The focus of this study was to elucidate the pharmacological anti-inflammatory effect of chitosan and chitosan and 5-ASA combinations in a murine experimental colitis model
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
