title: Liposomal encapsulation of dexamethasone modulates cytotoxicity, inflammatory cytokine response, and migratory properties of primary human macrophages.
abstract: The encapsulation of drugs into liposomes aims to enhance their efficacy and reduce their toxicity. Corticosteroid-loaded liposomes are currently being evaluated in patients suffering from rheumatoid arthritis, atherosclerosis, colitis, and cancer. Here, using several different fluorophore-labeled formulations, we comprehensively studied the impact of liposome encapsulation of the prototypic corticosteroid dexamethasone on various primary human cells in vitro. Liposomal dexamethasone targeted several primary cell types in a dose and time-dependent manner, but specifically reduced cytotoxicity against human fibroblasts and macrophages in comparison to the solute drug. Furthermore, macrophage maturation and polarization markers were altered. Interestingly, liposomal dexamethasone induced proinflammatory cytokine secretion (specifically TNF, IL1β, IL6) in unstimulated cells, but reduced this response under inflammatory conditions. Monocyte and macrophage migration was significantly inhibited by dexamethasone-loaded liposomes. The findings indicate that the encapsulation of dexamethasone into liposomes modulates their cellular mechanism of action, and provides important indications for follow-up in vivo investigations.
  
  
  BACKGROUND
  This study investigates mechanism of action of liposomal dexamethason in the treatment of inflammatory conditions. It is concluded that liposomal dexamethasone actually induces proinflammatory cytokine secretion in unstimulated cells, but reduces the same response under inflammatory conditions. Monocyte and macrophage migration was also inhibited. The findings indicate that liposomal dexamethasone may have different mechanisms of action than its native counterpart.
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany. Electronic address: mbartneck@ukaachen.de.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Franziska Marie
authors.initials: FM
authors.lastname: Peters
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Klaudia Theresa
authors.initials: KT
authors.lastname: Warzecha
authors.affiliation: Helmholtz-Institute for Biomedical Engineering, Biointerface Laboratory, RWTH Aachen, Germany.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bienert
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: van Bloois
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands; Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Department of Experimental Molecular Imaging, Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH University, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000494:pharmacology*; D002465:Cell Movement; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D003907:Dexamethasone / Q000008:administration & dosage* / Q000494:pharmacology*; D006801:Humans; D008081:Liposomes; D008264:Macrophages / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D008081:Liposomes; D003907:Dexamethasone
keywords: Cell activation; Cell migration; Corticosteroids; Cytokine release; Dexamethasone; Glucocorticoids; Immune cells; Inflammation; Liposomes; Primary human macrophages