title: Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases.
abstract: Liposomes are routinely used carrier materials for delivering drug molecules to pathological sites. Besides in tumors and inflammatory sites, liposomes also strongly accumulate in liver and spleen. The potential of using liposomes to treat acute and chronic liver disorders, however, has not yet been evaluated. We here explored the therapeutic potential of dexamethasone (Dex)-loaded liposomes for inflammatory liver diseases, using experimental models of acute and chronic liver injury in mice. Fluorescently labeled liposomes predominantly accumulated in hepatic phagocytes, but also in T cells. Importantly, Dex-loaded liposomes reduced T cells in blood and liver, more effectively than free Dex, and endorsed the anti-inflammatory polarization of hepatic macrophages. In experimental chronic liver damage, Dex-loaded liposomes significantly reduced liver injury and liver fibrosis. In immune-mediated acute hepatitis Dex-loaded liposomes, but not free Dex, significantly reduced disease severity. T cells, not macrophages, were significantly depleted by Dex liposomes in liver disease models in vivo, as further supported by mechanistic cell death in vitro studies. Our data indicate that Dex liposomes may be an interesting treatment option for liver diseases, in particular for immune-mediated hepatitis. The depletion of T cells might represent the major mechanism of action of Dex liposomes, rather than their macrophage-polarizing activities.
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Bartneck
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Katharina M
authors.initials: KM
authors.lastname: Scheyda
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Klaudia T
authors.initials: KT
authors.lastname: Warzecha
authors.affiliation: Department of Experimental Molecular Imaging (ExMI), Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Larissa Y
authors.initials: LY
authors.lastname: Rizzo
authors.affiliation: Institute of Pathology, University Bonn, Sigmund-Freud-Str. 25, 53127 Bonn, Germany.
authors.forename: Kanishka
authors.initials: K
authors.lastname: Hittatiya
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.affiliation: Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UPIS), Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Gert
authors.initials: G
authors.lastname: Storm
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Experimental Molecular Imaging (ExMI), Helmholtz Institute for Biomedical Engineering, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany; Department of Controlled Drug Delivery, MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, PO Box 217, 7500 AE Enschede, The Netherlands; Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UPIS), Universiteitsweg 99, 3584 CG Utrecht, The Netherlands.
authors.forename: Twan
authors.initials: T
authors.lastname: Lammers
authors.affiliation: Department of Medicine III, Medical Faculty, RWTH Aachen, Pauwelsstr. 30, 52074 Aachen, Germany. Electronic address: frank.tacke@gmx.net.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005453:Fluorescence; D006505:Hepatitis / Q000188:drug therapy / Q000473:pathology; D056747:Immunomodulation / Q000187:drug effects; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D008081:Liposomes; D008099:Liver / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy / Q000473:pathology; D008107:Liver Diseases / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008810:Mice, Inbred C57BL; D009928:Organ Specificity / Q000187:drug effects; D013601:T-Lymphocytes / Q000187:drug effects; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D008081:Liposomes; D003907:Dexamethasone
keywords: Dexamethasone; Liposomes; Liver fibrosis; Liver injury; Macrophages; T cells