{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T14:59:15Z","timestamp":1789570755751,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T00:00:00Z","timestamp":1765065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004505","name":"University of Catania","doi-asserted-by":"crossref","award":["UPB: 57722172155"],"award-info":[{"award-number":["UPB: 57722172155"]}],"id":[{"id":"10.13039\/501100004505","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Diroximel fumarate (DRF) is an orally administered prodrug used in multiple sclerosis (MS) treatment. Although it exhibits better gastrointestinal (GI) tolerability than its analogues, many patients still discontinue therapy due to frequent GI adverse events. To overcome these limitations, alternative drug delivery systems that bypass the GI tract are needed. Direct nose-to-brain delivery represents a promising approach to circumvent the blood\u2013brain barrier and target the central nervous system; however, limited nasal mucosal absorption and the small volume of the nasal cavity pose significant challenges. Solid lipid nanoparticles (SLNs) can potentially overcome these obstacles by enhancing drug bioavailability and protecting against enzymatic degradation. This research aimed to develop an innovative intranasal nanoformulation of DRF to improve brain targeting and patient compliance. DRF-loaded SLNs were prepared using a solvent-diffusion technique with stearic acid as the lipid phase and Poloxamer 188 as the surfactant. The obtained nanoparticles displayed favorable technological characteristics, with a mean diameter of 210 nm, a polydispersity index of 0.17, and a zeta potential of \u221236 mV, suggesting good long-term stability. Interactions between SLNs and biomembrane models (MLV) were also studied to elucidate their cellular uptake mechanism. Future work will focus on evaluating the in vivo efficacy of this novel nanoformulation.<\/jats:p>","DOI":"10.3390\/ijms262411827","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T08:21:43Z","timestamp":1765182103000},"page":"11827","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Diroximel Fumarate-Loaded Solid Lipid Nanoparticles (DRF-SLNs) as Potential Carriers for the Treatment of Multiple Sclerosis: Preformulation Study"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5322-5172","authenticated-orcid":false,"given":"Debora","family":"Santonocito","sequence":"first","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliana","family":"Greco","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-4754","authenticated-orcid":false,"given":"Maria Grazia","family":"Sarpietro","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2567-519X","authenticated-orcid":false,"given":"Aur\u00e9lie","family":"Schoubben","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, University of Perugia, Via del Giochetto 5, 06122 Perugia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-9562","authenticated-orcid":false,"given":"Claudia","family":"Sciacca","sequence":"additional","affiliation":[{"name":"Department of Chemical Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2160-4164","authenticated-orcid":false,"given":"Giuseppe","family":"Romeo","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katia","family":"Mangano","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Biotechnological Sciences, University of Catania, Via Santa Sofia 97, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7694-3641","authenticated-orcid":false,"given":"Carmelo","family":"Puglia","sequence":"additional","affiliation":[{"name":"Department of Drug and Health Sciences, University of Catania, Viale Andrea Doria 6, 95125 Catania, Italy"},{"name":"NANOMED\u2014Research Centre for Nanomedicine and Pharmaceutical Nanotechnology, Department of Drug and Health Sciences, University of Catania, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1177\/1352458520970841","article-title":"Rising Prevalence of Multiple Sclerosis Worldwide: Insights from the Atlas of MS, Third Edition","volume":"26","author":"Walton","year":"2020","journal-title":"Mult. 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