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Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, its clinical application is mainly limited by poor solubility, low bioavailability, and potential side effects. Herein a hepatic\u2010targeted nanodrugs composed of OCA and cholesterol\u2010lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier\u2010free nanocrystals (OCAHTs) are self\u2010assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter\u2010mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen\u2010challenged mice and high\u2010fat diet\u2010induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD\u2010associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter\u2010based strategy for hepatic\u2010targeting drug delivery but also presents an efficient and safe full\u2010API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.<\/jats:p>","DOI":"10.1002\/advs.202308866","type":"journal-article","created":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T01:55:07Z","timestamp":1704851707000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Hepatic\u2010Accumulated Obeticholic Acid and Atorvastatin Self\u2010Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic\u2010Associated Fatty Liver Disease"],"prefix":"10.1002","volume":"11","author":[{"given":"Huanfen","family":"Lu","sequence":"first","affiliation":[{"name":"School of Biomedical Sciences and Engineering South China University of Technology  Guangzhou Guangdong 511442 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