Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease
Abstract Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. Obeticholic acid (OCA), a selective farnesoid X receptor agonist, has been reported to ameliorate injury and inflammation in various liver diseases. However, i...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202308866 |
| _version_ | 1797263476592214016 |
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| author | Huanfen Lu Zhenglan Ban Kai Xiao Madi Sun Yongbo Liu Fangman Chen Tongfei Shi Li Chen Dan Shao Ming Zhang Wei Li |
| author_facet | Huanfen Lu Zhenglan Ban Kai Xiao Madi Sun Yongbo Liu Fangman Chen Tongfei Shi Li Chen Dan Shao Ming Zhang Wei Li |
| author_sort | Huanfen Lu |
| collection | DOAJ |
| description | Abstract Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. 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‐targeted nanodrugs composed of OCA and cholesterol‐lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier‐free nanocrystals (OCAHTs) are self‐assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter‐mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen‐challenged mice and high‐fat diet‐induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD‐associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter‐based strategy for hepatic‐targeting drug delivery but also presents an efficient and safe full‐API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD. |
| first_indexed | 2024-04-25T00:13:37Z |
| format | Article |
| id | doaj.art-98d6d4e306c34da2b6a9da13abef3ad9 |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-25T00:13:37Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-98d6d4e306c34da2b6a9da13abef3ad92024-03-13T07:30:35ZengWileyAdvanced Science2198-38442024-03-011110n/an/a10.1002/advs.202308866Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver DiseaseHuanfen Lu0Zhenglan Ban1Kai Xiao2Madi Sun3Yongbo Liu4Fangman Chen5Tongfei Shi6Li Chen7Dan Shao8Ming Zhang9Wei Li10School of Biomedical Sciences and Engineering South China University of Technology Guangzhou Guangdong 511442 ChinaNational Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology Guangzhou Guangdong 510006 ChinaNational Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology Guangzhou Guangdong 510006 ChinaSchool of Biomedical Sciences and Engineering South China University of Technology Guangzhou Guangdong 511442 ChinaCollege of Chinese Medicinal Materials Jilin Agricultural University Changchun 130118 ChinaNational Engineering Research Center for Tissue Restoration and Reconstruction South China University of Technology Guangzhou Guangdong 510006 ChinaSchool of Biomedical Sciences and Engineering South China University of Technology Guangzhou Guangdong 511442 ChinaCollege of Medicine Jilin University Changchun 130021 ChinaSchool of Biomedical Sciences and Engineering South China University of Technology Guangzhou Guangdong 511442 ChinaCollege of Medicine Jilin University Changchun 130021 ChinaCollege of Chinese Medicinal Materials Jilin Agricultural University Changchun 130118 ChinaAbstract Exploration of medicines for efficient and safe management of metabolic‐associated fatty liver disease (MAFLD) remains a challenge. 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‐targeted nanodrugs composed of OCA and cholesterol‐lowering atorvastatin (AHT) with an ideal active pharmaceutical ingredient (API) content for orally combined treatment of MAFLD is created. Such carrier‐free nanocrystals (OCAHTs) are self‐assembled, not only improving the stability in gastroenteric environments but also achieving hepatic accumulation through the bile acid transporter‐mediated enterohepatic recycling process. Orally administrated OCAHT outperforms the simple combination of OCA and AHT in ameliorating of liver damage and inflammation in both acetaminophen‐challenged mice and high‐fat diet‐induced MAFLD mice with less systematic toxicity. Importantly, OCAHT exerts profoundly reverse effects on MAFLD‐associated molecular pathways, including impairing lipid metabolism, reducing inflammation, and enhancing the antioxidation response. This work not only provides a facile bile acid transporter‐based strategy for hepatic‐targeting drug delivery but also presents an efficient and safe full‐API nanocrystal with which to facilitate the practical translation of nanomedicines against MAFLD.https://doi.org/10.1002/advs.202308866atorvastatininflammationmetabolic‐associated fatty liver diseasenanocrystalobeticholic acid |
| spellingShingle | Huanfen Lu Zhenglan Ban Kai Xiao Madi Sun Yongbo Liu Fangman Chen Tongfei Shi Li Chen Dan Shao Ming Zhang Wei Li Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease Advanced Science atorvastatin inflammation metabolic‐associated fatty liver disease nanocrystal obeticholic acid |
| title | Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease |
| title_full | Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease |
| title_fullStr | Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease |
| title_full_unstemmed | Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease |
| title_short | Hepatic‐Accumulated Obeticholic Acid and Atorvastatin Self‐Assembled Nanocrystals Potentiate Ameliorative Effects in Treatment of Metabolic‐Associated Fatty Liver Disease |
| title_sort | hepatic accumulated obeticholic acid and atorvastatin self assembled nanocrystals potentiate ameliorative effects in treatment of metabolic associated fatty liver disease |
| topic | atorvastatin inflammation metabolic‐associated fatty liver disease nanocrystal obeticholic acid |
| url | https://doi.org/10.1002/advs.202308866 |
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