Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

M. Bartneck, K.M. Scheyda, K.T. Warzecha, L.Y. Rizzo, K. Hittatiya, T. Luedde, Gerrit Storm, C. Trautwein, Twan Gerardus Gertudis Maria Lammers, F. Tacke

Research output: Contribution to journalArticleAcademicpeer-review

37 Citations (Scopus)

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.
Original languageUndefined
Pages (from-to)367-382
JournalBiomaterials
Volume37
DOIs
Publication statusPublished - 2015

Keywords

  • IR-99926
  • METIS-315199

Cite this

Bartneck, M., Scheyda, K. M., Warzecha, K. T., Rizzo, L. Y., Hittatiya, K., Luedde, T., ... Tacke, F. (2015). Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. Biomaterials, 37, 367-382. https://doi.org/10.1016/j.biomaterials.2014.10.030
Bartneck, M. ; Scheyda, K.M. ; Warzecha, K.T. ; Rizzo, L.Y. ; Hittatiya, K. ; Luedde, T. ; Storm, Gerrit ; Trautwein, C. ; Lammers, Twan Gerardus Gertudis Maria ; Tacke, F. / Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. In: Biomaterials. 2015 ; Vol. 37. pp. 367-382.
@article{cd38dc7b58894f1f87e59ba25cbd3a1d,
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.",
keywords = "IR-99926, METIS-315199",
author = "M. Bartneck and K.M. Scheyda and K.T. Warzecha and L.Y. Rizzo and K. Hittatiya and T. Luedde and Gerrit Storm and C. Trautwein and Lammers, {Twan Gerardus Gertudis Maria} and F. Tacke",
year = "2015",
doi = "10.1016/j.biomaterials.2014.10.030",
language = "Undefined",
volume = "37",
pages = "367--382",
journal = "Biomaterials",
issn = "0142-9612",
publisher = "Elsevier",

}

Bartneck, M, Scheyda, KM, Warzecha, KT, Rizzo, LY, Hittatiya, K, Luedde, T, Storm, G, Trautwein, C, Lammers, TGGM & Tacke, F 2015, 'Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases' Biomaterials, vol. 37, pp. 367-382. https://doi.org/10.1016/j.biomaterials.2014.10.030

Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases. / Bartneck, M.; Scheyda, K.M.; Warzecha, K.T.; Rizzo, L.Y.; Hittatiya, K.; Luedde, T.; Storm, Gerrit; Trautwein, C.; Lammers, Twan Gerardus Gertudis Maria; Tacke, F.

In: Biomaterials, Vol. 37, 2015, p. 367-382.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases

AU - Bartneck, M.

AU - Scheyda, K.M.

AU - Warzecha, K.T.

AU - Rizzo, L.Y.

AU - Hittatiya, K.

AU - Luedde, T.

AU - Storm, Gerrit

AU - Trautwein, C.

AU - Lammers, Twan Gerardus Gertudis Maria

AU - Tacke, F.

PY - 2015

Y1 - 2015

N2 - 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.

AB - 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.

KW - IR-99926

KW - METIS-315199

U2 - 10.1016/j.biomaterials.2014.10.030

DO - 10.1016/j.biomaterials.2014.10.030

M3 - Article

VL - 37

SP - 367

EP - 382

JO - Biomaterials

JF - Biomaterials

SN - 0142-9612

ER -