{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:02:48Z","timestamp":1789981368777,"version":"4.0.1"},"reference-count":43,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T00:00:00Z","timestamp":1789862400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Ministry of Education","doi-asserted-by":"publisher","award":["2021R1I1A3A0403710411"],"award-info":[{"award-number":["2021R1I1A3A0403710411"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/objectives: Febuxostat (FBXT), a xanthine oxidase (XO) inhibitor, is a urate-lowering drug commonly used to treat gout. XO is also a promising therapeutic target for inflammatory bowel disease (IBD). This study aimed to improve the efficacy and safety of FBXT repurposed for the treatment of IBD. Methods: FBXT was conjugated with the acidic amino acids aspartic acid (Asp) and glutamic acid (Glu) via amide linkages to yield the colon-specific conjugates FBXT-Asp and FBXT-Glu. Results: The results revealed that amino acid conjugation decreased the distribution coefficient of FBXT from 1.451 to \u22121.217 for FBXT-Asp and \u22120.859 for FBXT-Glu. In parallel, conjugation retarded FBXT transport across the small intestinal wall, with a more pronounced effect observed with Glu conjugation than with Asp conjugation. The conjugates were converted to FBXT in cecal contents under a nitrogen atmosphere while remaining intact in pH 1.2 buffer and small intestinal contents. The cecal conversion percentages at 8 and 24 h were 7.1% and 22%, respectively, for FBXT-Asp and 17% and 54.8%, respectively, for FBXT-Glu. Consistent with these in vitro results, oral gavage of FBXT-Glu resulted in greater FBXT accumulation in the rat cecum than that observed with free FBXT. In rats with 2,4-dinitrobenzenesulfonic acid-induced colitis, oral gavage of FBXT-Glu at a dose equivalent to 20 mg of FBXT ameliorated colonic damage and inflammation. This effect was more potent than that of FBXT at the same dose or sulfasalazine (SSZ), a currently used anti-IBD drug. Additionally, FBXT-Glu did not produce detectable blood levels of FBXT, whereas FBXT was detected at concentrations of up to 6.7 \u03bcM at 2 h after oral gavage of FBXT at the corresponding dose. Conclusions: FBXT-Glu may serve as an anti-colitis agent with therapeutic and toxicological advantages over FBXT and could be a viable alternative to SSZ.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091187","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1187","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Colon-Specific Delivery of Febuxostat via an Amino Acid Conjugate Enhances Anti-Colitis Efficacy and Limits Systemic Exposure"],"prefix":"10.3390","volume":"18","author":[{"given":"Suji","family":"Kim","sequence":"first","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Sanghyun","family":"Ju","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"}]},{"given":"Yunjin","family":"Jung","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea"},{"name":"Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,20]]},"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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