Nanocapsules generated out of a polymeric dexamethasone shell suppress the inflammatory response of liver macrophages

Dexamethasone (DXM) is a synthetic glucocorticoid with anti-inflammatory properties. Targeted delivery of dexamethasone to inflammatory cells, e. g. macrophages and Kupffer cells represents a promising approach to minimize side effects. The aim of the present study was to induce a targeted transport of novel DXM-based biodegradable nanocapsules to phagocytic cells. Nanocapsules (NCs) consisting of a hydroxyethylated glucose polymer (hydroxyethyl starch, HES) shell with encapsulated DXM and NCs synthesized exclusively in inverse miniemulsion out of DXM were investigated. Non-parenchymal murine liver cells served as target cells. HES-DXM NCs were predominantly incorporated by Kupffer cells (KCs). In contrast, DXM NCs were phagocytized by KCs and endothelial cells. The release of the NC-content was confirmed by incorporation of CellTracker (TM) into the NCs. Uptake of DXM NCs by Kupffer cells reduced significantly the release of inflammatory cytokines in response to LPS stimulation. Importantly, the DXM NCs consisting exclusively out of a dexamethasone shell offer the potential to serve as carriers for additional therapeutics. From the Clinical Editor: In this paper, nanocapsule-based targeted delivery of dexamethasone to inflammatory cells is presented as a promising approach to minimize side effects and increase efficacy of this anti-inflammatory clinically used corticosteroid. (C) 2013 Elsevier Inc. All rights reserved.