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Adv."],"published-print":{"date-parts":[[2026,10,23]]},"abstract":"<jats:p>The therapeutic options for patients with inflammatory bowel disease (IBD) have recently expanded substantially. Tofacitinib, an oral small-molecule inhibitor of Janus kinase (JAK), recently FDA approved for ulcerative colitis, represented a paradigm shift in a field previously dominated by biologics. Tofacitinib, however, carries a black box warning for major adverse cardiovascular events, an elevated risk of malignancies, risk of blood clots, and pulmonary embolism. In addition, tofacitinib is avoided in pregnancy and used with caution in women of child bearing age due to potential risks to the developing fetus. Notably, these potential complications are all due to the systemic distribution of tofacitinib. To address these issues, we developed Lipo-tm-HA, a liposomal platform incorporating mannitol (m) and hyaluronic acid (HA) for targeting tofacitinib (t) to the inflamed colon. We characterized Lipo-tm-HA and have shown that it (i) remains stable in gastric conditions due to HA coating, (ii) adheres to transferrin in inflamed mucosa due to its negative charge, and (iii) enhances macrophage uptake through mannose receptor\u2013mediated endocytosis. Due to targeting, we show that a single oral administration of Lipo-tm-HA at a dose of 10\u00a0milligrams per kilogram is superior in efficacy compared with daily treatment with free tofacitinib in a dextran sodium sulfate\u2013induced colitis model. Collectively, our innovative formulation will enable colonic inflammation targeting, reduce systemic exposure, and allow administration of decreased doses.<\/jats:p>","DOI":"10.1126\/sciadv.aeb1963","type":"journal-article","created":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T17:58:42Z","timestamp":1792778322000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["An innovative colon inflammation-targeting platform for ulcerative colitis treatment"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5609-7540","authenticated-orcid":true,"given":"Waliul","family":"Islam","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiming","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4498-9466","authenticated-orcid":true,"given":"Ling","family":"Li","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7251-1916","authenticated-orcid":true,"given":"Kevan J.","family":"Salimian","sequence":"additional","affiliation":[{"name":"Department of Pathology, School of Medicine, Johns Hopkins University, Baltimore, MD 21224, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7990-8238","authenticated-orcid":true,"given":"Florin M.","family":"Selaru","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."},{"name":"Department of Oncology, Sidney Kimmel Cancer Center, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."},{"name":"The Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, MD 21231, USA."},{"name":"Department of Biomedical Engineering, School of Medicine, Johns Hopkins University, Baltimore, MD 21231, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(19)30333-4"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izae020.081"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izab230"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2024.06.049"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606910"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2019.1657404"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ibd\/izad242"},{"key":"e_1_3_2_9_2","doi-asserted-by":"crossref","first-page":"175628481984863","DOI":"10.1177\/1756284819848631","article-title":"Tofacitinib in the treatment of ulcerative colitis: Efficacy and safety from clinical trials to real-world experience","volume":"12","author":"D\u2019Amico F.","year":"2019","unstructured":"F. 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