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The chemicals C<jats:sub>6<\/jats:sub>I, TC1, and TC2 were reported as promising antileishmanial drugs. We aimed to develop a topical nanoformulation that enhances the advantageous effect of C<jats:sub>6<\/jats:sub>I, TC1, and TC2, guaranteeing higher stability and bioavailability of the pharmacologically active components through the topical route. Nanoemulsions were prepared by ultrasonication based on oleic acid (0.5\u2009g). A relation of Tween\u00ae\u201080\/ethanol (1:3) and water was obtained; physicochemical characterization of all formulations was performed, and the preliminary stability and transdermal penetration of these nanoemulsions were also investigated. Newtonian\u2010type fluids with high load capacity, 147\u2013273\u2009nm globule size, and \u221215 to \u221218\u2009mV zeta potential were obtained with differential permeability rates in the first pig ear skin assay, first\u2010order kinetics\u2010release model for C<jats:sub>6<\/jats:sub>I, and Weibull for TC1 and TC2. The nanoemulsion showed\u00a0good stability, high encapsulation efficiency, and higher leishmanicidal activity against <jats:italic>Leishmania braziliensis<\/jats:italic> with lower cytotoxicity in U937 macrophages. In conclusion, nanoemulsions of ethanol\u2013oleic acid\/Tween\u00ae\u201080 increase the activity of compounds with leishmanicidal activity by increasing their penetration and sustained release.<\/jats:p>","DOI":"10.1002\/ardp.202300108","type":"journal-article","created":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T18:37:21Z","timestamp":1681756641000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Nanoemulsions for increased penetrability and sustained release of leishmanicidal compounds"],"prefix":"10.1002","volume":"356","author":[{"given":"Darlyn J.","family":"Garc\u00eda","sequence":"first","affiliation":[{"name":"PECET \u2010 Facultad de Medicina Universidad de Antioquia Medell\u00edn Colombia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maritza","family":"Fern\u00e1ndez\u2010Culma","sequence":"additional","affiliation":[{"name":"PECET \u2010 Facultad de Medicina Universidad de 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