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

Nanomedicine (Lond). 2019 Sep;14(18):2409-2422. doi: 10.2217/nnm-2018-0496. Epub 2019 Aug 28.


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.

Keywords: Alzheimer’s disease; chitosan nanocapsules; nanomedicine; nasal administration; p38 MAPK.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intranasal
  • Alzheimer Disease / drug therapy
  • Alzheimer Disease / metabolism
  • Animals
  • Benzamides / administration & dosage*
  • Benzamides / pharmacokinetics
  • Benzamides / therapeutic use
  • Brain / drug effects*
  • Brain / metabolism
  • Cell Line
  • Chitosan / chemistry*
  • Disease Models, Animal
  • Drug Delivery Systems
  • Female
  • Male
  • Mice
  • Nanocapsules / chemistry*
  • Protein Kinase Inhibitors / administration & dosage*
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use
  • Pyridones / administration & dosage*
  • Pyridones / pharmacokinetics
  • Pyridones / therapeutic use
  • Rats, Wistar
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism


  • Benzamides
  • Nanocapsules
  • PH 797804
  • Protein Kinase Inhibitors
  • Pyridones
  • Chitosan
  • p38 Mitogen-Activated Protein Kinases