{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:49:02Z","timestamp":1786121342958,"version":"build-2736575974"},"reference-count":59,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T00:00:00Z","timestamp":1785888000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","award":["UID\/04567\/2025"],"award-info":[{"award-number":["UID\/04567\/2025"]}]},{"award":["UID\/04567\/2025"],"award-info":[{"award-number":["UID\/04567\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"COFAC\/ILIND"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Innovative topical delivery systems are needed to improve the stability, loading capacity, and performance of poorly water-soluble bioactive compounds. TransfersomILs, hybrid nanosystems combining transfersomes with ionic liquids (ILs), represent a promising strategy for this purpose. This work assessed the effect of incorporating cholinium-based ILs into transfersomal formulations loaded with hydroxycinnamic acids (HCAs)\u2014ferulic, caffeic, and p-coumaric acids. Methods: TransfersomILs were prepared by the thin-film hydration method followed by sonication, with or without HCA incorporation. Formulations were characterised in terms of physicochemical properties, storage stability and impact on keratinocyte viability. In vitro release, permeation, and occlusion studies were also performed. Results: IL incorporation significantly improved formulation performance. TransfersomILs showed smaller vesicle sizes and more negative zeta potential values than conventional transfersomes, indicating improved physicochemical characteristics. ILs also increased association efficiency and loading capacity for all HCAs, although the magnitude depended on both the IL and the compound. Release profiles were compound-dependent, reflecting distinct release kinetics due to variable HCA\u2013IL\u2013membrane interactions. Permeation studies showed enhanced HCA flux across both silastic and human epidermal membranes compared with aqueous solutions and\/or conventional transfersomes, with [Cho][Gly] generally showing superior performance. All formulations demonstrated acceptable cytocompatibility and occlusive properties. Conclusions: The combination of transfersomes and cholinium-based ILs demonstrated a synergistic effect, highlighting transfersomILs as a versatile platform for improving the topical delivery of HCAs.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080962","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T09:16:22Z","timestamp":1785921382000},"page":"962","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["TransfersomILs: A Synergy to Boost the Skin Delivery of Hydroxycinnamic Acids"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3129-6495","authenticated-orcid":false,"given":"Ana","family":"J\u00falio","sequence":"first","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta B.","family":"Martins","sequence":"additional","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Martinho","sequence":"additional","affiliation":[{"name":"ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o","family":"Vieira","sequence":"additional","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"},{"name":"Universidad de Alcal\u00e1, Departamento de Ci\u00eancias Biom\u00e9dicas, Ctra. Madrid-Barcelona km. 33,600, 28805 Alcal\u00e1 de Henares, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1333-9137","authenticated-orcid":false,"given":"Nuno","family":"Saraiva","sequence":"additional","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6429-6213","authenticated-orcid":false,"given":"Catarina","family":"Rosado","sequence":"additional","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5407-3983","authenticated-orcid":false,"given":"Catarina","family":"Pereira-Leite","sequence":"additional","affiliation":[{"name":"CBIOS, ECTS, Universidade Lus\u00f3fona, Campo Grande, 376, 1749-024 Lisboa, Portugal"},{"name":"Laborat\u00f3rio Associado para a Qu\u00edmica Verde (LAQV), REQUIMTE (Rede de Qu\u00edmica e Tecnologia), Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira n. 228, 4050-313 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3278","DOI":"10.1021\/acs.molpharmaceut.3c00126","article-title":"Natural Ingredients of Transdermal Drug Delivery Systems as Permeation Enhancers of Active Substances through the Stratum Corneum","volume":"20","author":"Schafer","year":"2023","journal-title":"Mol. 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