{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:02:53Z","timestamp":1789981373208,"version":"4.0.1"},"reference-count":97,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"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":["2024-FAR.L_DOCPAS_DA"],"award-info":[{"award-number":["2024-FAR.L_DOCPAS_DA"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2024-FAR.L_DOCPAS_DA"],"award-info":[{"award-number":["2024-FAR.L_DOCPAS_DA"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background: Dimethyl fumarate (DMF) is an approved therapeutic agent for the treatment of multiple sclerosis, known for its anti-inflammatory and neuroprotective properties. However, its oral administration is often accompanied by gastrointestinal side effects, limiting its therapeutic potential. In the present study, a novel nanoemulsion (NE) formulation was developed and characterized with the aim of enhancing DMF exposure in the cerebrospinal fluid (CSF) following intranasal administration. Methods: The formulation was prepared via a self-emulsification method using geraniol (GER) as the oil phase, selected for its antioxidant properties, and chitosan oleate as a mucoadhesive stabilizer and absorption promoter. Physicochemical characterization, in vitro release, RPMI 2650 cell cytotoxicity, and permeability were evaluated. Finally, an optimized NE (1.08 \u00b1 0.02 mg\/mL DMF and 0.28 \u00b1 0.01 mg\/mL GER) was administered intranasally to adult male Sprague\u2013Dawley rats to assess DMF and GER exposure in the CSF. Results: The NEs exhibited optimal physicochemical properties: a mean particle size of approximately 170 nm, a polydispersity index below 0.3, and a positive zeta potential (above 20 mV). Spectroscopic and thermal analyses confirmed GER and DMF compatibility and a reciprocal enhancement of stability. In vitro drug release studies revealed a fast release profile, with 81% of DMF released within 2 h, aligning with the rapid absorption expected from nasal administration. Cytotoxicity assays showed high biocompatibility (&gt;86% viability up to 50 \u00b5M DMF), while permeability studies demonstrated significant absorption, with 60% of DMF and 90% of GER absorbed within 2\u20133 h, favored by smaller droplet size. In rats, intranasal delivery achieved maximum CSF concentrations of ~8 \u00b5g\/mL for DMF and ~1.5 \u00b5g\/mL for GER within 2 h. Conclusions: These findings provide pharmacokinetic proof-of-concept supporting further investigation of this intranasal formulation for CNS delivery of DMF.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091168","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"1168","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-9174-6320","authenticated-orcid":false,"given":"Eleonora Sofia","family":"Cama","sequence":"first","affiliation":[{"name":"Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, 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