Inhibition of p38 MAPK in the Brain Through Nasal Administration of p38 Inhibitor Loaded in Chitosan Nanocapsules
Álvaro Casadomé‐Perales, Laura De Matteis, María Alleva, Cristina Infantes-Rodríguez, Irene Palomares-Pérez, Takashi Saito, Takaomi C. Saido, José A. Esteban, Ángel R. Nebreda, Jesús M. de la Fuente, Carlos G. Dotti · Nanomedicine · 2019
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.