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Four VCZ-loaded hyalurosomal formulations were prepared (H1-H4) by modulating the proportions of phospholipid and polyols. Although changes in some physicochemical properties were observed, all the VCZ-loaded nanosystems were nanosized (&lt;\u2009140\u00a0nm), spherical, multilamellar and exhibited high entrapments efficiencies (&gt;\u200972%), excellent biocompatibility with human keratinocytes and potent antifungal activity against\n                    <jats:italic>C. albicans<\/jats:italic>\n                    . VCZ release from formulation H1 (1% phospholipid, 10% ethanol) followed a Fickian mechanism, while H2\u2013H4 (4\u201310% phospholipid, 2.5\u201310% ethanol) exhibited anomalous diffusion involving both diffusion and matrix relaxation or erosion. Additionally, H1 and H2 (1\u20134% of phospholipid, 10% ethanol) achieved significantly enhanced drug penetration into deeper skin layers and superior in vivo antifungal efficacy compared to VCZ dispersion. The results highlight the potential of hyalurosomes as a next-generation topical antifungal delivery system, effective against both superficial and invasive candidiasis, with formulations H1 and H2 emerging as the most promising candidates for the treatment of the more invasive forms.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Graphical abstract<\/jats:bold>\n                  <\/jats:p>","DOI":"10.1007\/s13346-025-02007-3","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T18:34:14Z","timestamp":1762799654000},"page":"2089-2105","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Novel voriconazole-loaded hyalurosomes optimized for enhanced skin penetration and antifungal activity against Candida albicans"],"prefix":"10.1007","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1707-7966","authenticated-orcid":false,"given":"Amparo","family":"N\u00e1cher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4811-239X","authenticated-orcid":false,"given":"Jos\u00e9-Esteban","family":"Peris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9816-9693","authenticated-orcid":false,"given":"Raquel","family":"Tal\u00e9ns-Visconti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4214-8567","authenticated-orcid":false,"given":"Octavio","family":"D\u00edez-Sales","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3787-257X","authenticated-orcid":false,"given":"Maria Letizia","family":"Manca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4818-2344","authenticated-orcid":false,"given":"Maria","family":"Manconi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5786-5668","authenticated-orcid":false,"given":"Iris","family":"Usach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"issue":"1","key":"2007_CR1","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/j.jaad.2019.09.066","volume":"82","author":"S Mehrmal","year":"2020","unstructured":"Mehrmal S, Uppal P, Giesey RL, Delost GR. 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