{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:41:28Z","timestamp":1785894088488,"version":"3.56.0"},"reference-count":110,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"\u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara"},{"id":[{"id":"https:\/\/ror.org\/00afdp487","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Gels"],"abstract":"<jats:p>The skin serves as the first line of defense, being highly prone to external damage. Silibinin (SIL) exerts skin-protective properties, but its topical use requires a suitable delivery system. Despite the growing interest in proniosomal platforms loaded with natural products, their application for the cutaneous delivery of SIL remains scarcely explored. This study proposes the pharmaco-technical characterization and preclinical safety evaluation of a SIL-loaded proniosomal gel (SIL-PG) for skin application. SIL-PG was produced using the coacervation phase separation technique, analyzed in terms of physicochemical and technological properties, and evaluated in vitro and in ovo for potential cytotoxic and irritant effects. SIL-PG retained a yellowish, creamy aspect, proper rheological behavior and spreadability, gradual in vitro drug release, sustained permeation, and an adequate safety profile, evidenced by the lack of cytotoxicity in HaCaT keratinocytes and spheroids and the absence of irritant potential in 3D EpiDerm\u2122 reconstructed human tissues and on the chorioallantoic membrane. Overall, these findings emphasize SIL-PG as a potential pharmaceutical formulation for dermal use, with favorable pharmaco-technical characteristics and in vitro\u2013in ovo biocompatibility.<\/jats:p>","DOI":"10.3390\/gels12060504","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T17:18:16Z","timestamp":1780679896000},"page":"504","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Silibinin-Loaded Proniosomal Gel for Cutaneous Application: Pharmaco-Technical Characterization and In Vitro\u2013In Ovo Biocompatibility"],"prefix":"10.3390","volume":"12","author":[{"given":"Andreea","family":"Smeu","sequence":"first","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"Research Center for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"University Clinic of Toxicology, Drug Industry, Management, Legislation, and Dermatopharmacy, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Olariu","sequence":"additional","affiliation":[{"name":"Department II\u2014Pharmaceutical Technology, Formulation and Technology of Drugs Research Center, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3292-9079","authenticated-orcid":false,"given":"Iasmina","family":"Marcovici","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"University Clinic of Toxicology, Drug Industry, Management, Legislation, and Dermatopharmacy, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Haj-Ali","sequence":"additional","affiliation":[{"name":"Doctoral School, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"Research Center for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"University Clinic of Toxicology, Drug Industry, Management, Legislation, and Dermatopharmacy, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lavinia","family":"Vlaia","sequence":"additional","affiliation":[{"name":"Department II\u2014Pharmaceutical Technology, Formulation and Technology of Drugs Research Center, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicen\u021biu","family":"Vlaia","sequence":"additional","affiliation":[{"name":"Department II\u2014Organic Chemistry, Formulation and Technology of Drugs Research Center, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"T\u0103nase","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raluca Mioara","family":"Cosoroab\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Dental Medicine, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0529-1911","authenticated-orcid":false,"given":"Vlad","family":"Socoliuc","sequence":"additional","affiliation":[{"name":"Laboratory of Magnetic Fluids, Center of Fundamental and Advanced Technical Research, Romanian Academy\u2013Timisoara Branch, 24 Mihai Viteazul Avenue, 300223 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina Adriana","family":"Dehelean","sequence":"additional","affiliation":[{"name":"Research Center for Pharmaco-Toxicological Evaluation, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"},{"name":"University Clinic of Toxicology, Drug Industry, Management, Legislation, and Dermatopharmacy, Faculty of Pharmacy, \u201cVictor Babes\u201d University of Medicine and Pharmacy Timisoara, Eftimie Murgu Square No. 2, 300041 Timisoara, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Baker, P., Huang, C., Radi, R., Moll, S.B., Jules, E., and Arbiser, J.L. 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