title: Nanocapsules generated out of a polymeric dexamethasone shell suppress the inflammatory response of liver macrophages.
abstract: 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™ 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Children's hospital, Johannes-Gutenberg University, Mainz, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Fichter
authors.forename: Grit
authors.initials: G
authors.lastname: Baier
authors.forename: Marvin
authors.initials: M
authors.lastname: Dedters
authors.forename: Leah
authors.initials: L
authors.lastname: Pretsch
authors.forename: Anette
authors.initials: A
authors.lastname: Pietrzak-Nguyen
authors.forename: Katharina
authors.initials: K
authors.lastname: Landfester
authors.forename: Stephan
authors.initials: S
authors.lastname: Gehring
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology; D016503:Drug Delivery Systems; D005260:Female; D006895:Hydroxyethyl Starch Derivatives / Q000737:chemistry*; D007728:Kupffer Cells / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000737:chemistry*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D006895:Hydroxyethyl Starch Derivatives; D053769:Nanocapsules; D003907:Dexamethasone
keywords: Cytokines; Dexamethasone nanocapsules; Kupffer cells; Liver sinusoid endothelial cells