Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation

Cama, Eleonora Sofia; Botti, Giada; Perteghella, Sara; Catenacci, Laura; Tareen, Fahad Khan; Beggiato, Sarah; Bonferoni, Maria Cristina; Ferraro, Luca; Sorrenti, Milena; Dalpiaz, Alessandro

doi:10.3390/pharmaceutics18091168

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Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation

by

Eleonora Sofia Cama

^1,†

,

Giada Botti

^2,†

,

Sara Perteghella

¹

,

Laura Catenacci

^1,*

,

Fahad Khan Tareen

¹

,

Sarah Beggiato

³,

Maria Cristina Bonferoni

¹

,

Luca Ferraro

³

,

Milena Sorrenti

^1,‡

and

Alessandro Dalpiaz

^2,‡

¹

Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy

²

Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, Via Fossato di Mortara 19, 44121 Ferrara, Italy

³

Department of Life Sciences and Biotechnology, University of Ferrara, Via Borsari 46, 44121 Ferrara, Italy

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

These authors contributed equally to this work.

Pharmaceutics 2026, 18(9), 1168; https://doi.org/10.3390/pharmaceutics18091168

Submission received: 27 July 2026 / Revised: 9 September 2026 / Accepted: 13 September 2026 / Published: 16 September 2026

(This article belongs to the Special Issue Advances in Nanotechnology-Based Drug Delivery Systems, 2nd Edition)

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Abstract

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 ± 0.02 mg/mL DMF and 0.28 ± 0.01 mg/mL GER) was administered intranasally to adult male Sprague–Dawley 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 (>86% viability up to 50 µM DMF), while permeability studies demonstrated significant absorption, with 60% of DMF and 90% of GER absorbed within 2–3 h, favored by smaller droplet size. In rats, intranasal delivery achieved maximum CSF concentrations of ~8 µg/mL for DMF and ~1.5 µg/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.

Keywords: nanoemulsion; dimethyl fumarate; nose-to-brain drug delivery; geraniol; multiple sclerosis; chitosan oleate

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MDPI and ACS Style

Cama, E.S.; Botti, G.; Perteghella, S.; Catenacci, L.; Tareen, F.K.; Beggiato, S.; Bonferoni, M.C.; Ferraro, L.; Sorrenti, M.; Dalpiaz, A. Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation. Pharmaceutics 2026, 18, 1168. https://doi.org/10.3390/pharmaceutics18091168

AMA Style

Cama ES, Botti G, Perteghella S, Catenacci L, Tareen FK, Beggiato S, Bonferoni MC, Ferraro L, Sorrenti M, Dalpiaz A. Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation. Pharmaceutics. 2026; 18(9):1168. https://doi.org/10.3390/pharmaceutics18091168

Chicago/Turabian Style

Cama, Eleonora Sofia, Giada Botti, Sara Perteghella, Laura Catenacci, Fahad Khan Tareen, Sarah Beggiato, Maria Cristina Bonferoni, Luca Ferraro, Milena Sorrenti, and Alessandro Dalpiaz. 2026. "Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation" Pharmaceutics 18, no. 9: 1168. https://doi.org/10.3390/pharmaceutics18091168

APA Style

Cama, E. S., Botti, G., Perteghella, S., Catenacci, L., Tareen, F. K., Beggiato, S., Bonferoni, M. C., Ferraro, L., Sorrenti, M., & Dalpiaz, A. (2026). Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation. Pharmaceutics, 18(9), 1168. https://doi.org/10.3390/pharmaceutics18091168

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Mucoadhesive Nanoemulsions for Nose-to-Brain Delivery of Dimethyl Fumarate: Development, Characterization and Proof-of-Concept In Vivo Evaluation

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