Dexamethasone palmitate nanoparticles: an efficient treatment for severe inflammation

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Presentation Time: 03:15 PM - 04:30 PM
Poster Board Number: B576
Abstract ID: 4902

Presenting Author:
laila EMAM , PhD Student at Univ. Paris Saclay

Abstract:

Studies in patients with sepsis suggest that corticosteroids reduce mortality by 6%, but untargeted systemic corticosteroid administration may cause side effects. Thus, we have developed new lipid-based Nanoparticles loaded with Dexamethasone palmitate (NDex) that enable the local delivery of corticosteroids into the primary site of infection with the goal of improving their therapeutic effect and reducing their unwanted off-target effects.

6 hours post lipopolysaccharide administration (22 mg/kg), adult mice received NDex (1 mg/kg) by endotracheal administration, and the analyses were realized 16 hours later.  The results demonstrated a significant beneficial effect of NDex on model severity. Compared to LPS group, the immune response of lung macrophages in LPS+NDex group was modulated with reductions in phagocytosis, cytokine release, and expression of specific markers. A significant effect was also observed on neutrophil activity through a decrease in phagocytosis and extracellular trap formation. Higher RNA expression levels of DUSP-1 and GILZ were also measured in lung suggesting the induction of immune-suppressive pathways. Importantly biodistribution analyses showed that endotracheally administered nanoparticles did not relocate into the systemic circulation. In conclusion, NDex reproduced the beneficial effects of dexamethasone phosphate on immune cells and even improved part of them, without distributing into the blood preventing potential associated side effects.