{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T15:41:14Z","timestamp":1785426074416,"version":"3.56.0"},"reference-count":59,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32260243"],"award-info":[{"award-number":["32260243"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["32260243"],"award-info":[{"award-number":["32260243"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004607","name":"Natural Science Foundation of Guangxi Province","doi-asserted-by":"publisher","award":["2025GXNSFHA069260"],"award-info":[{"award-number":["2025GXNSFHA069260"]}],"id":[{"id":"10.13039\/501100004607","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Hepatic fibrosis is characterized by the abnormal activation of hepatic stellate cells (HSCs) and excessive deposition of the extracellular matrix. Currently, effective clinical therapeutic strategies remain limited. Modulating ferroptosis-related pathways in activated HSCs has emerged as a promising therapeutic target for hepatic fibrosis treatment. Methods: An amphiphilic copolymer was synthesized by conjugating COS with ART, which spontaneously self-assembled into micelles; subsequent modification with retinoic acid (RA) yielded RA-functionalized ART\u2013COS copolymer micelles. Curcumin was selected as a model drug to evaluate the potential of the micelles in enhancing intestinal epithelial transport, oral absorption and bioavailability. Meanwhile, in vitro targeting ability, capacity to modulate ferroptosis in HSCs and in vivo therapeutic efficacy were systematically investigated. Results: The RA-functionalized ART\u2013COS micelles significantly enhanced intestinal epithelial drug transport, oral absorption, and bioavailability. In vitro experiments demonstrated that the micelles preferentially accumulate in activated HSCs, inhibit GPX4 expression, and induce excessive ROS production and ferroptosis, thereby effectively attenuating hepatic fibrosis. In vivo studies confirmed that the micelles regulated extracellular matrix metabolism, reduced collagen deposition, suppressed the activation and proliferation of HSCs, and ultimately helped attenuate hepatic fibrosis progression. Conclusions: This study successfully developed RA-functionalized ART\u2013COS copolymer micelles. The micelles improve the accumulation of artesunate in liver tissue and yield favorable anti-fibrotic effects, thereby providing a promising translational strategy for anti-fibrotic therapy.<\/jats:p>","DOI":"10.3390\/pharmaceutics18060682","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T07:58:38Z","timestamp":1780473518000},"page":"682","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Preparation of Oral Artesunate-Chitosan Oligosaccharide\u2013Retinoic Acid Copolymer Micelles for Attenuating Hepatic Fibrosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Shiyuan","family":"Lin","sequence":"first","affiliation":[{"name":"Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China"},{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feixian","family":"Lu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiao","family":"Li","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kefeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Chen","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Guilin Medical University, Guilin 541199, China"},{"name":"Key Laboratory of Pharmacology for Prevention and Treatment of High Incidence Diseases in Guangxi Higher Education Institutions, Guilin Medical University, Guilin 541199, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxin","family":"Wang","sequence":"additional","affiliation":[{"name":"Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou 510405, China"},{"name":"Department of Pharmaceutics, School of Pharmacy, Fudan University and Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai 201203, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1002\/hep.32285","article-title":"Hepatic fibrosis 2022: Unmet needs and a blueprint for the future","volume":"75","author":"Friedman","year":"2022","journal-title":"Hepatology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.jhep.2018.12.003","article-title":"Fibrosis and alcohol-related liver disease","volume":"70","author":"Lackner","year":"2019","journal-title":"J. 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