{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T18:19:06Z","timestamp":1789841946571,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Faisal University","award":["KFU263625"],"award-info":[{"award-number":["KFU263625"]}]},{"award":["KFU263625"],"award-info":[{"award-number":["KFU263625"]}],"id":[{"id":"https:\/\/ror.org\/00dn43547","id-type":"ROR","asserted-by":"publisher"}]},{"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>Objectives: The present study was designed to repurpose aripiprazole (AR) as an antifungal drug for the management of topical candidiasis using a bioadhesive sponge incorporating a hyaluronic acid (HA)-, ceramide-, and terpene-based vesicular nanosystem (HCT-NS). Methods: AR-loaded HCT-NS were formulated by the modified ethanol injection method with varying amounts of HA, ceramide, and two types of terpenes. The formulation optimization of AR-loaded HCT-NS was carried out by a full factorial design. The responses evaluated were zeta potential (ZP), particle size (PS), and entrapment efficiency (EE). Results: The optimized AR-loaded HCT-NS has 5 mg of HA, 10 mg of ceramide, and fenchone, which showed spherical vesicles with EE of 81.21 \u00b1 0.01%, PS of 223.25 \u00b1 11.25 nm, polydispersity index (PDI) of 0.492 \u00b1 0.003, and ZP of \u221227.74 \u00b1 0.04 mV. The optimum HCT-NS showed a greater drug release in comparison to the AR suspension. In addition, the selected HCT-NS exhibited good bioadhesive characteristics and stayed stable during storage. Confocal laser scanning microscopy confirmed the penetration of the fluorescently optimized HCT-NS via the skin. Further, the scanning electron microscope image indicates the porous structure of the formed sponge. In vivo evaluations for the optimum HCT-NS sponge showed a good antifungal impact against Candida albicans. The safety of topical treatment was confirmed by histopathological examination. Conclusions: Taken together, the results here suggest that the AR-loaded HCT-NS sponge showed potent antifungal activity against Candida albicans fungal infection.<\/jats:p>","DOI":"10.3390\/ph19081135","type":"journal-article","created":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T15:05:42Z","timestamp":1784819142000},"page":"1135","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Repurposed Aripiprazole-Loaded Hyaluronic Acid\/Ceramide\/Terpene Nanosponge as a Bioadhesive Topical Delivery System for Cutaneous Candida albicans Infection"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1775-264X","authenticated-orcid":false,"given":"Rofida","family":"Albash","sequence":"first","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2850-8669","authenticated-orcid":false,"given":"Anroop B.","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6752-9094","authenticated-orcid":false,"given":"Mohamed A.","family":"Morsy","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-1549","authenticated-orcid":false,"given":"Katharigatta N.","family":"Venugopala","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4245-0803","authenticated-orcid":false,"given":"Pottathil","family":"Shinu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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, Suez 43511, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4195-6036","authenticated-orcid":false,"given":"Amira B.","family":"Kassem","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacy Practice, Faculty of Pharmacy, Damnhour University, Damanhur 22516, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1804","DOI":"10.1038\/s41564-025-02055-y","article-title":"Evolution of antifungal resistance in the environment","volume":"10","author":"Rhodes","year":"2025","journal-title":"Nat. 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