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Based on its anti\u2010inflammatory, antiproliferative and anti\u2010melanoma attributes, the fungal metabolite kojic acid represents an attractive candidate for anti\u2010psoriatic research. The present work aims to investigate an efficient topical bio\u2010friendly vesicular system loaded with kojic acid isolated from <jats:italic>Aspergillus oryzae<\/jats:italic> as an alternative way for the management of psoriasis to avoid systemic toxicity. Kojic acid\u2010loaded spanlastics were prepared by ethanol injection technique, employing span 60 along with brij 35 and cremophor rh40 as edge activators, with the complete in vitro characterization of the developed nanoplatform. The selected formulation displayed a spherical morphology, an optimum particle size of 234.2\u2009\u00b1\u20091.65\u2009nm, high entrapment efficiency (87.4%\u2009\u00b1\u20090.84%) and significant sustained drug release compared with the drug solution. In vivo studies highlighted the superior relief of psoriasis symptoms and the ability to maintain healthy skin with the least changes in mRNA expression of inflammatory cytokines, achieved by the developed nanoplatform compared to kojic acid solution. Moreover, the in vivo histopathological studies confirmed the safety of the topically applied spanlastics. In addition, the molecular mechanism was approached through in vitro assessment of cathepsin S and PDE\u20104 inhibitory activities and in silico investigation of kojic acid docking in several anti\u2010psoriatic drug targets. Our results suggest that a topically applied vesicular system loaded with kojic acid could lead to an expansion in the dermo\u2010cosmetic use of kojic acid as a natural bio\u2010friendly alternative for systemic anti\u2010psoriatic drugs.<\/jats:p>","DOI":"10.1002\/ardp.202400410","type":"journal-article","created":{"date-parts":[[2024,8,24]],"date-time":"2024-08-24T02:30:52Z","timestamp":1724466652000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Green preparation and evaluation of the anti\u2010psoriatic activity of vesicular elastic nanocarriers of kojic acid from <i>Aspergillus oryzae<\/i> N12: Repurposing of a dermo\u2010cosmetic lead"],"prefix":"10.1002","volume":"357","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7818-3319","authenticated-orcid":false,"given":"Ashaimaa Y.","family":"Moussa","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Faculty of Pharmacy Ain\u2010Shams University Cairo Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidy","family":"Abbas","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, Faculty of Pharmacy Damanhour University Damanhour Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1930-9361","authenticated-orcid":false,"given":"Mariam","family":"Zewail","sequence":"additional","affiliation":[{"name":"Pharmaceutics Department, Faculty of Pharmacy Damanhour University Damanhour Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Passent M. 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