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

AuthorsCasadomé-Perales, Álvaro; Matteis, Laura de; Alleva, María; Infantes-Rodríguez, Cristina; Palomares-Pérez, Irene; Saito, Takashi; Saido, Takaomi C.; Esteban, José A. ; Nebreda, Angel R.; Fuente, Jesús M. de la; Dotti, Carlos G.
Issue Date2019
PublisherFuture Medicine
CitationNanomedicine 14(18): 2409-2422 (2019)
Abstract[Aim]: 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.
[Materials & methods]: 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 in vitro and in ex vivo and in vivo systems, in a mouse model of Alzheimer’s disease.
[Results]: Encapsulated inhibitor retains enzymatic inhibitory activity and tissue penetration capacity in vitro, ex vivo and in vivo.
[Conclusion]: 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.
Publisher version (URL)https://doi.org/10.2217/nnm-2018-0496
Appears in Collections:(ICMA) Artículos
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