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Oral drug delivery system is a promising approach for treating UC, but it often fails to accumulate to the inflammatory lesions, thus, it is impressive to develop a colon-targeted oral delivery system for preventing systemic toxicity and maintaining UC therapeutics. Here, a negative-charged PLGA nanoparticle system was designed to encapsulate celastrol (Cel), and then chitosan and mannose were coated on the surface of the nanoparticles (MC@Cel-NPs) to endow these nanoparticles with the mucosal adsorption and macrophage targeting abilities. MC@Cel-NPs demonstrate excellent resist decomposition ability against the strong acidic gastrointestinal environment, and accumulates in the specific inflammatory sites through the affinity of electrostatic reaction. After releasing the payload, MC@Cel-NPs could remarkably alleviate the colon inflammation, which was evidenced by the decrease in pro-inflammatory cytokines TNF-\u03b1, IL-1\u03b2, and IL-6 in both blood and colon sections, and scavenging reactive oxygen species (ROS) in colon cells, including macrophage, neutrophil, T cell, and B cell. This nanoparticle system provided a new approach for treating UC through a Chinese herbal ingredient-related oral delivery manner.<\/jats:p>","DOI":"10.1177\/20417314241265892","type":"journal-article","created":{"date-parts":[[2024,8,10]],"date-time":"2024-08-10T23:36:26Z","timestamp":1723332986000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":20,"title":["Oral delivery of pH-sensitive nanoparticles loaded Celastrol targeting the inflammatory colons to treat ulcerative colitis"],"prefix":"10.1177","volume":"15","author":[{"given":"Yue","family":"Zhao","sequence":"first","affiliation":[{"name":"School of Pharmacology, Guangdong Medical University, Dongguan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinlian","family":"Yao","sequence":"additional","affiliation":[{"name":"School of Pharmacology, Guangdong Medical University, Dongguan, 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