Nose-to-Brain Delivery of Dexamethasone: Biodistribution Studies in Mice

Abstract

Neuroinflammation (NI) is an important physiological process which promotes the tissue repair and homeostatic maintenance in the central nervous system (CNS) after different types of insults. However, when it is exacerbated and sustained in time, NI plays a critical role in the pathogenesis of different neurological diseases. The high systemic doses required for brain-specific targeting leads to severe undesirable effects. The intranasal (IN) route has been proposed as an alternative drug administration route for a better NI control. Herein, the brain biodistribution of intranasally administered dexamethasone (Dex) versus intravenous administered one is reported. A higher amount of dexamethasone was found in every brain analyzed regions of those brains of intranasally administered mice. HPLC analysis also revealed that IN administration allows Dx arrives faster and in a greater concentration to the brain in comparison with intravenous administration, data confirmed by immunofluorescence and HPLC analysis. These data support the proposal of the IN administration of Dx as an alternative for a more efficiently control of NI. Significance Statement This work highlights the biodistribution of dexamethasone after its intranasal administration. Intranasal administration allows for a faster arrival, better distribution and a higher concentration of the drug within the brain compared to its intravenous administration. These results explain some of the evidence shown by us in a previous work in which dexamethasone controls neuroinflammation in a murine stroke model and can be used to propose alternative treatments for neuroinflammatory diseases.