Inhibition of p38 MAPK in the brain through nasal administration of p38 inhibitor loaded in chitosan nanocapsules

To determine whether a p38 MAPK inhibitor incorporated into nanoemulsion-based chitosan nanocapsules can reduce the activity of this kinase in the brain through their nasal administration in mice. We selected the p38 MAPK inhibitor PH797804, an ATP-competitive inhibitor of p38α encapsulated in nanoe...

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Bibliographic Details
Published in:Nanomedicine (London, England) England), 2019-09, Vol.14 (18), p.2409-2422
Main Authors: Casadomé-Perales, Álvaro, Matteis, Laura De, Alleva, Maria, Infantes-Rodríguez, Cristina, Palomares-Pérez, Irene, Saito, Takashi, Saido, Takaomi C, Esteban, José A, Nebreda, Angel R, de la Fuente, Jesús M, Dotti, Carlos G
Format: Article
Language:English
Subjects:
Alzheimer’s disease
chitosan nanocapsules
nanomedicine
nasal administration
p38 MAPK
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Summary:To determine whether a p38 MAPK inhibitor incorporated into nanoemulsion-based chitosan nanocapsules can reduce the activity of this kinase in the brain through their nasal administration in mice. We selected the p38 MAPK inhibitor PH797804, an ATP-competitive inhibitor of p38α encapsulated in nanoemulsion-based chitosan nanocapsules. Biological effect was evaluated in microglial and neuronal cells and in and systems, in a mouse model of Alzheimer’s disease. Encapsulated inhibitor retains enzymatic inhibitory activity and tissue penetration capacity and . Nasal administration of chitosan nanocapsules can be an effective approach for brain-restricted reduction of p38 MAPK activity, thus reducing the side effects of systemic administration.
ISSN:1743-5889
1748-6963
DOI:10.2217/nnm-2018-0496