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Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery

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Title: Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery
Authors: Kiilerich, Kat F, Andresen, Trine, Darbani, Behrooz, Gregersen, Laura H K, Liljensøe, Anette, Bennike, Tue B, Holm, René, Moeller, Jesper B, Andersen, Vibeke
Source: Kiilerich, K F, Andresen, T, Darbani, B, Gregersen, L H K, Liljensøe, A, Bennike, T B, Holm, R, Moeller, J B & Andersen, V 2025, 'Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery', International Journal of Molecular Sciences, vol. 26, no. 2, 575. https://doi.org/10.3390/ijms26020575
Publication Year: 2025
Collection: University of Southern Denmark: Research Output / Syddansk Universitet
Subject Terms: Humans, Immunity, Innate/drug effects, Inflammatory Bowel Diseases/drug therapy, Drug Delivery Systems/methods, Animals, Reactive Oxygen Species/metabolism, Extracellular Traps/metabolism, Neutrophils/metabolism
Description: Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly-without systemic absorption-could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.
Document Type: article in journal/newspaper
File Description: application/pdf
Language: English
DOI: 10.3390/ijms26020575
Availability: https://portal.findresearcher.sdu.dk/da/publications/bf0a901e-ed56-440e-8d03-1d1a794980bd
https://doi.org/10.3390/ijms26020575
https://findresearcher.sdu.dk/ws/files/282985518/ijms-26-00575.pdf
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.3A569FD4
Database: BASE
Description
Abstract:Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30-50% of patients or cause significant side effects, emphasizing the need for new treatments. Targeting the innate immune system and enhancing drug delivery to inflamed gut regions are promising strategies. Neutrophils play a central role in IBD by releasing reactive oxygen species (ROS) and neutrophil extracellular traps (NETs) -DNA-based structures with cytotoxic proteins-that contribute to mucosal damage and inflammation. Recent studies linking ROS production, DNA repair, and NET formation have identified NETs as potential therapeutic targets, with preclinical models showing positive outcomes from NET inhibition. Innovative oral drug delivery systems designed to target gut inflammation directly-without systemic absorption-could improve treatment precision and reduce side effects. Advanced formulations utilize properties such as particle size, surface modifications, and ROS-triggered release to selectively target the distal ileum and colon. A dual strategy that combines a deeper understanding of IBD pathophysiology to identify inflammation-related therapeutic targets with advanced drug delivery systems may offer significant promise. For instance, pairing NET inhibition with ROS-responsive nanocarriers could enhance treatment efficacy, though further research is needed. This synergistic approach has the potential to greatly improve outcomes for IBD patients.
DOI:10.3390/ijms26020575