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Ascorbyl palmitate\u2010based vesicles (aspasomes) can be considered a promising nanocarrier for dermal and transdermal delivery due to their skin whitening properties and suitable delivery of payloads through the skin. The aim of this study was the synthesis of multidrug Idebenone\/naproxen co\u2010loaded aspasomes for the development of an effective anti\u2010inflammatory nanomedicine. Aspasomes had suitable physicochemical properties and were safe <jats:italic>in\u2005vivo<\/jats:italic> if topically applied on human healthy volunteers. Idebenone\/naproxen co\u2010loaded aspasomes demonstrated an increased therapeutic efficacy of payloads compared to the commercially available Naprosyn\u00ae gel, with a rapid decrease of chemical\u2010induced erythema on human volunteers. These promising results strongly suggested a potential application of Idebenone\/naproxen multidrug aspasomes for the development of an effective skin anti\u2010inflammatory therapy.<\/jats:p>","DOI":"10.1002\/cmdc.202200067","type":"journal-article","created":{"date-parts":[[2022,2,23]],"date-time":"2022-02-23T04:59:13Z","timestamp":1645592353000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Multidrug Idebenone\/Naproxen Co\u2010loaded Aspasomes for Significant in\u2005vivo Anti\u2010inflammatory Activity"],"prefix":"10.1002","volume":"17","author":[{"given":"Nicola","family":"d'Avanzo","sequence":"first","affiliation":[{"name":"Department of Pharmacy University \u201cG. d'Annunzio\u201d of Chieti-Pescara  Via dei Vestini n.31 66100 Chieti Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Chiara","family":"Cristiano","sequence":"additional","affiliation":[{"name":"Department of 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