{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T09:06:28Z","timestamp":1788944788122,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004242","name":"Princess Nourah bint Abdulrahman University","doi-asserted-by":"publisher","award":["PNURSP2026R91"],"award-info":[{"award-number":["PNURSP2026R91"]}],"id":[{"id":"10.13039\/501100004242","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PNURSP2026R91"],"award-info":[{"award-number":["PNURSP2026R91"]}],"id":[{"id":"https:\/\/ror.org\/05b0cyh02","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background\/Objectives: Cutaneous fungal infections remain a major therapeutic challenge due to poor skin penetration and emerging antifungal resistance of current treatments. Drug repurposing offers a promising strategy to expand antifungal therapy, with ketoprofen (KPN) recently demonstrating antifungal activity. Methods: In this study, KPN-cationic aspasomes (Ca-ASPMs) were developed using a Quality by Design (QbD) approach to enhance topical delivery and maximize the therapeutic potential of repurposed KPN. A D-optimal experimental design was implemented to investigate the influence of ascorbyl palmitate amount (X1), ethanol concentration (X2), and cationic SAA type (X3) on the critical quality attributes of KPN-Ca-ASPMs, namely entrapment efficiency, particle size, and zeta potential. Results: Numerical optimization identified an optimum formulation comprising 10 mg ascorbyl palmitate, 5% ethanol, and didodecyldimethylammonium bromide (DDAB) as cationic SAA, with an overall desirability of 0.815. The optimal KPN-Ca-ASPM (F9) exhibited nanosized vesicles (213.24 \u00b1 2.20 nm) and 91.30 \u00b1 10.01% entrapment efficiency. TEM confirmed the spherical morphology of the vesicles, while DSC demonstrated successful incorporation of KPN within the aspasomal matrix. F9 exhibited enhanced in vitro drug release (68% after 6 h) and excellent storage stability. Confocal laser scanning microscopy demonstrated enhanced skin penetration of F9. In a murine cutaneous candidiasis model, F9 significantly enhanced the antifungal efficacy of KPN, producing a 2.989-log reduction in fungal burden compared with the untreated group and significantly outperforming the free drug (p = 0.0005). Histopathological examination confirmed restoration of normal skin architecture. Conclusions: Collectively, the QbD-guided development of KPN-Ca-ASPM provided a reproducible nanocarrier that significantly enhanced the topical antifungal efficacy of repurposed KPN, highlighting its potential for the treatment of cutaneous candidiasis.<\/jats:p>","DOI":"10.3390\/ph19091394","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T14:35:29Z","timestamp":1788359729000},"page":"1394","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Quality by Design-Guided Development of Ketoprofen-Cationic Aspasomes Unlocks the Antifungal Potential of Repurposed Ketoprofen for Topical Therapy"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5918-9870","authenticated-orcid":false,"given":"Moaz A","family":"Eltabeeb","sequence":"first","affiliation":[{"name":"Department of Industrial Pharmacy, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST), Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-264X","authenticated-orcid":false,"given":"Rofida","family":"Albash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics, College of Pharmaceutical Sciences and Drug Manufacturing, Misr University for Science and Technology (MUST), Giza 12585, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7972-9827","authenticated-orcid":false,"given":"Mariam","family":"Hassan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"},{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Galala University, New Galala City 43511, Suez, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0190-9502","authenticated-orcid":false,"given":"Sadek","family":"Ahmed","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"software","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3635-9093","authenticated-orcid":false,"given":"Ahmed M.","family":"Agiba","sequence":"additional","affiliation":[{"name":"School of Engineering and Sciences, Tecnol\u00f3gico de Monterrey, Monterrey 64849, Mexico"},{"name":"R&D Directorate, MultiCare Egypt for Pharmaceutical Industries S.A.E., Industrial Area, New Cairo 3, Cairo 11511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3726-0386","authenticated-orcid":false,"given":"Azza A. K.","family":"El-Sheikh","sequence":"additional","affiliation":[{"name":"Basic Health Sciences Department, College of Medicine, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"given":"Diana E.","family":"Aziz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1080\/1040841X.2020.1843399","article-title":"Exploiting solid lipid nanoparticles and nanostructured lipid carriers for drug delivery against cutaneous fungal infections","volume":"47","author":"Araujo","year":"2021","journal-title":"Crit. 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