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At present, the existing drugs for the treatment of cytokine storm have limited efficacy and severe adverse effects. Here, we report a lymphatic targeting self\u2010microemulsifying drug delivery system containing baicalein to effectively inhibit cytokine storm. Baicalein self\u2010microemulsion with phospholipid complex as an intermediate carrier (BAPC\u2010SME) prepared in this study could be spontaneously emulsified to form 12\u2010nm oil\u2010in\u2010water nanoemulsion after administration. And then BAPC\u2010SME underwent uptake by enterocyte through endocytosis mediated by lipid valve and clathrin, and had obvious characteristics of mesenteric lymph node targeting distribution. Oral administration of BAPC\u2010SME could significantly inhibit the increase in plasma levels of 14 cytokines: TNF\u2010\u03b1, IL\u20106, IFN\u2010\u03b3, MCP\u20101, IL\u201017A, IL\u201027, IL\u20101\u03b1, GM\u2010CSF, MIG, IFN\u2010\u03b2, IL\u201012, MIP\u20103\u03b1, IL\u201023, and RANTES in mice experiencing systemic cytokine storm. BAPC\u2010SME could also significantly improve the pathological injury and inflammatory cell infiltration of lung tissue in mice experiencing local cytokine storm. This study does not only provide a new lymphatic targeted drug delivery strategy for the treatment of cytokine storm but also has great practical significance for the clinical development of baicalein self\u2010microemulsion therapies for cytokine storm.<\/jats:p>","DOI":"10.1002\/btm2.10357","type":"journal-article","created":{"date-parts":[[2022,6,20]],"date-time":"2022-06-20T08:33:38Z","timestamp":1655714018000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Baicalein self\u2010microemulsion based on drug\u2013phospholipid complex for the alleviation of cytokine storm"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1854-5514","authenticated-orcid":false,"given":"Hengfeng","family":"Liao","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Ye","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfang","family":"Lian","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Liu","sequence":"additional","affiliation":[{"name":"Research and Development Department Beijing Wehand\u2010Bio Pharmaceutical Co. 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