{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:58:50Z","timestamp":1777971530150,"version":"3.51.4"},"reference-count":50,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,6]],"date-time":"2022-08-06T00:00:00Z","timestamp":1659744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"publisher","award":["FAR 2020"],"award-info":[{"award-number":["FAR 2020"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Research Foundation","award":["FAR 2020"],"award-info":[{"award-number":["FAR 2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In this study, transethosomes were investigated as potential delivery systems for dimethyl fumarate. A formulative study was performed investigating the effect of the composition of transethosomes on the morphology and size of vesicles, as well as drug entrapment capacity, using cryogenic transmission electron microscopy, photon correlation spectroscopy, and HPLC. The stability of vesicles was evaluated, both for size increase and capability to control the drug degradation. Drug release kinetics and permeability profiles were evaluated in vitro using Franz cells, associated with different synthetic membranes. The in vitro viability, as well as the capacity to improve wound healing, were evaluated in human keratinocytes. Transmission electron microscopy enabled the evaluation of transethosome uptake and intracellular fate. Based on the obtained results, a transethosome gel was further formulated for the cutaneous application of dimethyl fumarate, the safety of which was evaluated in vivo with a patch test. It was found that the phosphatidylcholine concentration affected vesicle size and lamellarity, influencing the capacity to control dimethyl fumarate\u2019s chemical stability and release kinetics. Indeed, phosphatidylcholine 2.7% w\/w led to multivesicular vesicles with 344 nm mean size, controlling the drug\u2019s chemical stability for at least 90 days. Conversely, phosphatidylcholine 0.9% w\/w resulted in 130 nm sized unilamellar vesicles, which maintained 55% of the drug over 3 months. These latest kinds of transethosomes were able to improve wound healing in vitro and were easily internalised by keratinocytes. The selected transethosome gel, loading 25 mg\/mL dimethyl fumarate, was not irritant after cutaneous application under occlusion, suggesting its possible suitability in the treatment of wounds caused by diabetes mellitus or peripheral vascular diseases.<\/jats:p>","DOI":"10.3390\/ijms23158756","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T22:51:46Z","timestamp":1659912706000},"page":"8756","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Dimethyl Fumarate-Loaded Transethosomes: A Formulative Study and Preliminary Ex Vivo and In Vivo Evaluation"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9096-0560","authenticated-orcid":false,"given":"Francesca","family":"Ferrara","sequence":"first","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mascia","family":"Benedusi","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Cervellati","sequence":"additional","affiliation":[{"name":"Department of Neurosciences and Rehabilitation, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2100-2043","authenticated-orcid":false,"given":"Maddalena","family":"Sguizzato","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leda","family":"Montesi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnese","family":"Bondi","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7192-7821","authenticated-orcid":false,"given":"Markus","family":"Drechsler","sequence":"additional","affiliation":[{"name":"Bavarian Polymer Institute (BPI) Keylab \u201cElectron and Optical Microscopy\u201d, University of Bayreuth, D-95440 Bayreuth, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter","family":"Pula","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8792-0947","authenticated-orcid":false,"given":"Giuseppe","family":"Valacchi","sequence":"additional","affiliation":[{"name":"Animal Science Department, Plants for Human Health Institute, NC Research Campus, NC State University, Kannapolis, NC 28081, USA"},{"name":"Department of Environmental Sciences and Prevention, University of Ferrara, I-44121 Ferrara, Italy"},{"name":"Department of Food and Nutrition, Kyung Hee University, Seoul 02447, Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8416-3629","authenticated-orcid":false,"given":"Elisabetta","family":"Esposito","sequence":"additional","affiliation":[{"name":"Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, I-44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/01.prs.0000222562.60260.f9","article-title":"Wound healing: An overview","volume":"117","author":"Broughton","year":"2006","journal-title":"Plast. 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