{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T18:59:18Z","timestamp":1793213958674,"version":"4.5.0"},"reference-count":58,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,17]],"date-time":"2026-05-17T00:00:00Z","timestamp":1778976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008809","name":"University of Ha'il","doi-asserted-by":"publisher","award":["RG-24072"],"award-info":[{"award-number":["RG-24072"]}],"id":[{"id":"10.13039\/501100008809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RG-24072"],"award-info":[{"award-number":["RG-24072"]}],"id":[{"id":"https:\/\/ror.org\/013w98a82","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objective: The introduction of Ketoconazole (KZ, Nizoral\u00ae) in 1977 by Janssen Pharmaceutica marked a significant milestone in medical mycology as the first broad-spectrum oral antifungal agent. However, KZ is a highly lipophilic compound, presenting significant challenges in the development of efficient topical formulations. Moreover, oral KZ has undergone labeling revisions and market withdrawal due to serious hepatic side effects. This study aimed to design, optimize, and evaluate KZ-loaded nanoemulsions (NEs; KZ-NEs) as a delivery platform that could improve skin bioavailability and antifungal activity. Methods: Optimized KZ-NEs were converted to a mucoadhesive formulation (KZ-NEC) by the addition of Carbopol\u00ae 940 NF to enhance the adherence of the formulations to the skin surface. NEs were evaluated concerning physical appearance, globule size, polydispersity index, zeta potential, pH, viscosity, and drug content. Optimized KZ-NE and lead KZ-NEC formulations were further evaluated for in vitro release, ex vivo skin permeation and deposition, skin irritation, and in vivo studies. Results: In vitro release studies revealed that nanocarrier systems provided a sustained release of KZ over 24 h. The ex vivo permeability coefficients of KZ from the optimized KZ-NE and lead KZ-NEC formulations were approximately four- and three-fold greater than that achieved with the marketed cream formulation, respectively. In addition, the Cmax of the lead KZ-NEC formulation (14.4 \u00b1 1.1 \u03bcg\/mL) was significantly higher (p &lt; 0.05) compared with the marketed cream formulation (10.5 \u00b1 0.5 \u03bcg\/mL). Moreover, in vitro antifungal susceptibility testing showed that KZ demonstrated improved antifungal efficacy when incorporated into the KZ-NE and KZ-NEC formulations. Neither of the NE-based formulations caused any alterations in skin color or morphology during the 24 h visual observation period. Both NE-based formulations were stable for 90 days (the last time-point tested) at three different storage conditions. Conclusions: NE-based formulation could serve as an effective topical delivery platform for KZ and could improve therapeutic outcomes for patients with topical fungal infections.<\/jats:p>","DOI":"10.3390\/pharmaceutics18050612","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T16:39:34Z","timestamp":1779295174000},"page":"612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Ketoconazole-Loaded Mucoadhesive Nanoemulsions for the Better Management of Topical Fungal Infections: Optimization, In Vitro, Ex Vivo, and In Vivo Assessments"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2774-5128","authenticated-orcid":false,"given":"Mashan","family":"Almutairi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Adel Ali","family":"Youssef","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics & Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9212-7786","authenticated-orcid":false,"given":"Gehad M.","family":"Subaiea","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Alobaida","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4353-6043","authenticated-orcid":false,"given":"Sultan","family":"Almuntashiri","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, College of Pharmacy, University of Ha\u2019il, Ha\u2019il 81442, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2892","DOI":"10.2174\/1381612821666150428150456","article-title":"Topical Delivery of Drugs for the Effective Treatment of Fungal Infections of Skin","volume":"21","author":"Akhtar","year":"2015","journal-title":"Curr. 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