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Advanced drug delivery strategies, mainly including multifunctional polymer\/lipid\/protein-based organic nanoparticles, metal\/silica-based inorganic nanoparticles, vesicles represented by liposomes, and nanoemulsions, are expected to overcome these druggability hurdles of celastrol via oral, transdermal or intravenous administration. This review summarizes recent progress in a series of celastrol formulations, including novel dosage forms and delivery routes accompanied with consequential pharmacological effects and mechanisms of action, which have the potential to bring about better druggability conducive to future medical treatment.<\/jats:p>","DOI":"10.3390\/biom16070932","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T03:06:34Z","timestamp":1782875194000},"page":"932","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Overcoming the Druggability Hurdles of Celastrol: A Critical Review of Advanced Drug Delivery Strategies"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7170-7407","authenticated-orcid":false,"given":"Keren","family":"Xu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science & Jianxing Honors College, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang-Egypt Joint Laboratory on Intelligent Discovery of Marine Drugs, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science & Jianxing Honors College, Zhejiang University of Technology, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0058-060X","authenticated-orcid":false,"given":"Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science & Jianxing Honors College, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang-Egypt Joint Laboratory on Intelligent Discovery of Marine Drugs, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5414-9300","authenticated-orcid":false,"given":"Xuanrong","family":"Sun","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science & Jianxing Honors College, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang-Egypt Joint Laboratory on Intelligent Discovery of Marine Drugs, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4176-2071","authenticated-orcid":false,"given":"Zhikun","family":"Yang","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science & Jianxing Honors College, Zhejiang University of Technology, Hangzhou 310014, China"},{"name":"Zhejiang-Egypt Joint Laboratory on Intelligent Discovery of Marine Drugs, Hangzhou 310014, China"},{"name":"Zhejiang Key Laboratory of Green Manufacturing Technology for Chemical Drugs, Hangzhou 310014, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1016\/j.bbrc.2010.03.050","article-title":"Celastrol: Molecular Targets of Thunder God Vine","volume":"394","author":"Salminen","year":"2010","journal-title":"Biochem. 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