{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T22:08:11Z","timestamp":1790892491337,"version":"4.1.0"},"reference-count":122,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,1,11]],"date-time":"2025-01-11T00:00:00Z","timestamp":1736553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Inflammatory bowel disease (IBD), encompassing Crohn\u2019s disease and ulcerative colitis, involves chronic inflammation of the gastrointestinal tract. Current immune-modulating therapies are insufficient for 30\u201350% 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) \u2014DNA-based structures with cytotoxic proteins\u2014that 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\u2014without systemic absorption\u2014could 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.<\/jats:p>","DOI":"10.3390\/ijms26020575","type":"journal-article","created":{"date-parts":[[2025,1,13]],"date-time":"2025-01-13T07:40:08Z","timestamp":1736754008000},"page":"575","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Advancing Inflammatory Bowel Disease Treatment by Targeting the Innate Immune System and Precision Drug Delivery"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-8769-6968","authenticated-orcid":false,"given":"Kat F.","family":"Kiilerich","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trine","family":"Andresen","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg \u00d8, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0289-6392","authenticated-orcid":false,"given":"Behrooz","family":"Darbani","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura H. K.","family":"Gregersen","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3937-0095","authenticated-orcid":false,"given":"Anette","family":"Liljens\u00f8e","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4354-1731","authenticated-orcid":false,"given":"Tue B.","family":"Bennike","sequence":"additional","affiliation":[{"name":"Department of Health Science and Technology, The Faculty of Medicine, Aalborg University, 9220 Aalborg \u00d8, Denmark"},{"name":"Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4894-7765","authenticated-orcid":false,"given":"Ren\u00e9","family":"Holm","sequence":"additional","affiliation":[{"name":"Department of Physics, Chemistry and Pharmacy, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8786-8037","authenticated-orcid":false,"given":"Jesper B.","family":"Moeller","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark"},{"name":"Danish Institute for Advanced Study, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0127-2863","authenticated-orcid":false,"given":"Vibeke","family":"Andersen","sequence":"additional","affiliation":[{"name":"Molecular Diagnostic and Clinical Research Unit, University Hospital of Southern Denmark, 6200 Aabenraa, Denmark"},{"name":"Department of Regional Health Research, University of Southern Denmark, 5000 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,1,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2652","DOI":"10.1056\/NEJMra2002697","article-title":"Pathophysiology of Inflammatory Bowel Diseases","volume":"383","author":"Chang","year":"2020","journal-title":"N. 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