Fiche publication


Date publication

janvier 2025

Journal

International journal of pharmaceutics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr BEDUNEAU Arnaud


Tous les auteurs :
Otaegui L, Urgin T, Zaiter T, Zussy C, Vitalis M, Pellequer Y, Acar N, Vigor C, Galano JM, Durand T, Givalois L, Béduneau A, Desrumaux C

Résumé

Reduced docosahexaenoic acid (DHA) concentrations seem to be associated with an increased risk of Alzheimer's disease (AD), and DHA accretion to the brain across the blood-brain-barrier (BBB) can be modulated by various factors. Therefore, there is an urgent need to identify an efficient and non-invasive method to ensure brain DHA enrichment. In the present study, a safe and stable DHA-enriched nanoemulsion, designed to protect DHA against oxidation, was designed and administered intranasally in a transgenic mouse model of AD, the J20 mice. Intranasal treatment with nanoformulated DHA significantly improved well-being and working spatial memory in six-months-old J20 mice. These behavioral effects were associated with a reduction of amyloid deposition, oxidative stress, and neuroinflammation in brain tissues, which may be partially due to DHA-induced inactivation of the pleiotropic kinase GSK3β. In conclusion, intranasal DHA administration exhibited strong therapeutic effects and disease-modifying benefits in the J20 AD model. Given that DHA has already shown safety and tolerability in healthy human subjects, our results further support the need for clinical trials to assess the potential of this approach in Alzheimer's patients.

Mots clés

Alzheimer’s disease, Amyloid plaques, Docosahexaenoic acid, Intranasal administration, Nanoemulsion, Nanovectorization, Neuroinflammation, Omega-3 polyunsaturated fatty acids, Oxidative stress

Référence

Int J Pharm. 2025 01 7;:125125