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Here, a Sucralfate\u2010based oral formulation is developed that incorporates therapeutic nanoparticles and transforms into a paste\u2010like coacervate upon contact with intestinal fluid, uniformly coating the entire gastrointestinal tract within 6 h, and clearing through fecal transit by 12 h. Systematic investigation shows that nanoparticle hydrophobicity is essential for stable incorporation into Sucralfate\u2010based formulation, supporting compatibility with a wide range of nanoparticle types. The incorporated nanoparticles are stabilized by strong non\u2010covalent interactions, which limit gastric leaching and reduce cellular uptake by 0.044% compared with PEGylated nanoparticles. As a representative example, antioxidant cerium oxide nanoparticles are tested in two distinct oxidative stress\u2010related models of intestinal injury, including immune\u2010mediated colitis and radiation\u2010induced enteropathy. In DSS colitis, our system reduced weight loss from 17.2% to 2.2% and restored colon structure and oxidative\u2010stress injury. In radiation\u2010induced enteropathy, our system attenuated weight loss from 25.5% to 11.4%, doubled villus length, and markedly enhanced epithelial regeneration. The formulation also accommodates nanoparticles with imaging capability, demonstrating versatility for both therapeutic and diagnostic applications in gastrointestinal diseases.<\/jats:p>","DOI":"10.1002\/adma.202514708","type":"journal-article","created":{"date-parts":[[2026,1,3]],"date-time":"2026-01-03T06:10:23Z","timestamp":1767420623000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Orally Administered Nanoparticle Coacervate for Therapeutic Coating of Full Gastrointestinal Tract"],"prefix":"10.1002","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-5022-2218","authenticated-orcid":false,"given":"Yunjung","family":"Lee","sequence":"first","affiliation":[{"name":"Center For Nanoparticle Research Institute for Basic Science (IBS)  Seoul Republic of Korea"},{"name":"School of Chemical and Biological Engineering Institute of Chemical Processes Seoul National University  Seoul Republic of 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