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It was achieved through regular thin-film evaporation &amp; hydration techniques. To examine the effect of formulation parameters on menthosome characteristics, a 2<jats:sup>3<\/jats:sup> full factorial design was used\u00a0using Design-Expert\u00ae software. The optimized batch exhibited a vesicle size (107.6\u00a0nm), a polydispersity index (PDI) (0.248), entrapment efficiency (% EE) (76.9%), and a zeta potential (-33.7\u00a0mV). Results from <jats:italic>ex vivo<\/jats:italic> skin permeation studies and <jats:italic>in vitro<\/jats:italic> drug release demonstrated enhanced improved skin permeation and drug release compared to other formulations. An <jats:italic>in vitro<\/jats:italic>\u00a0antifungal and <jats:italic>in vivo<\/jats:italic>\u00a0pharmacodynamic study, elucidated the enhanced effectiveness of the optimized formulation against <jats:italic>Candida albicans<\/jats:italic>. In summary, menthosomes could serve as a potent vehicle to enhance drug penetration via the skin to improve its antifungal activity.<\/jats:p>\n          <jats:p>\n            <jats:bold>Graphical Abstract<\/jats:bold>\n          <\/jats:p>","DOI":"10.1208\/s12249-024-03021-3","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T17:44:17Z","timestamp":1736358257000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Menthol-based Novel Ultra-Deformable Vesicle: Formulation, Optimization and Evaluation of an Antifungal Drug"],"prefix":"10.1208","volume":"26","author":[{"given":"Hema","family":"Manjushree","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devika","family":"Nayak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Halagali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahalaxmi","family":"Rathnanand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan","family":"Tawale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koteshwara","family":"Ananthmurthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesil Mathew","family":"Aranjani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6540-9550","authenticated-orcid":false,"given":"Vamshi Krishna","family":"Tippavajhala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"3021_CR1","doi-asserted-by":"crossref","unstructured":"de Santos GCO, Vasconcelos CC, Lopes AJO, Cart\u00e1genes M do S de S, Filho AKDB, do Nascimento FRF, et al. 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