Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human primary macrophages to support chronic wound healing

Anne Gauthier, Andreas Fisch, Klaus Seuwen, Birgit Baumgarten, Heinz Ruffner, Alexandra Aebi, Martin Rausch, Fabian Kiessling, Matthias Bartneck, Ralf Weiskirchen, Frank Tacke, Gert Storm, Twan Lammers (Corresponding Author), Marie Gabrielle Ludwig (Corresponding Author)

Research output: Contribution to journalArticleAcademicpeer-review

5 Citations (Scopus)

Abstract

Glucocorticoids are well established anti-inflammatory agents, however, their use to treat chronic inflammatory diseases is limited due to a number of serious side effects. For example, long-term local treatment of chronic wounds with glucocorticoids is prohibited by dysregulation of keratinocyte and fibroblast function, leading to skin thinning. Here, we developed and tested liposome formulations for local delivery of dexamethasone to primary human macrophages, to drive an anti-inflammatory/pro-resolution phenotype appropriate for tissue repair. The liposomes were loaded with the pro-drug dexamethasone-phosphate and surface-modified with either polyethylene glycol or phosphatidylserine. The latter was used to mimic phosphatidylserine-harboring apoptotic cells, which are substrates for efferocytosis, an essential pro-resolution function. Both formulations induced a dexamethasone-like gene expression signature in macrophages, decreased IL6 and TNFα release, increased secretion of thrombospondin 1 and increased efferocytosis activity. Phosphatidylserine-modified liposomes exhibited a faster uptake, a higher potency and a more robust phenotype induction than polyethylene glycol-modified liposomes. Fibroblast and keratinocyte cell cultures as well as a 3D skin equivalent model showed that liposomes applied locally to wounds are preferentially phagocytosed by macrophages. These findings indicate that liposomes, in particular upon shell modification with phosphatidylserine, promote dexamethasone delivery to macrophages and induce a phenotype suitable to support chronic wound healing.

Original languageEnglish
Pages (from-to)481-495
Number of pages15
JournalBiomaterials
Volume178
DOIs
Publication statusPublished - 1 Sep 2018

Fingerprint

Liposomes
Macrophages
Wound Healing
Glucocorticoids
Phosphatidylserines
Phenotype
Dexamethasone
dexamethasone 21-phosphate
Fibroblasts
Keratinocytes
Polyethylene glycols
Skin
Anti-Inflammatory Agents
Thrombospondin 1
Wounds and Injuries
Prodrugs
Transcriptome
Phagocytosis
Cell culture
Gene expression

Keywords

  • Glucocorticoid
  • Liposomes
  • Macrophage
  • Targeted delivery
  • Wound healing

Cite this

Gauthier, Anne ; Fisch, Andreas ; Seuwen, Klaus ; Baumgarten, Birgit ; Ruffner, Heinz ; Aebi, Alexandra ; Rausch, Martin ; Kiessling, Fabian ; Bartneck, Matthias ; Weiskirchen, Ralf ; Tacke, Frank ; Storm, Gert ; Lammers, Twan ; Ludwig, Marie Gabrielle. / Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human primary macrophages to support chronic wound healing. In: Biomaterials. 2018 ; Vol. 178. pp. 481-495.
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Gauthier, A, Fisch, A, Seuwen, K, Baumgarten, B, Ruffner, H, Aebi, A, Rausch, M, Kiessling, F, Bartneck, M, Weiskirchen, R, Tacke, F, Storm, G, Lammers, T & Ludwig, MG 2018, 'Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human primary macrophages to support chronic wound healing' Biomaterials, vol. 178, pp. 481-495. https://doi.org/10.1016/j.biomaterials.2018.04.006

Glucocorticoid-loaded liposomes induce a pro-resolution phenotype in human primary macrophages to support chronic wound healing. / Gauthier, Anne; Fisch, Andreas; Seuwen, Klaus; Baumgarten, Birgit; Ruffner, Heinz; Aebi, Alexandra; Rausch, Martin; Kiessling, Fabian; Bartneck, Matthias; Weiskirchen, Ralf; Tacke, Frank; Storm, Gert; Lammers, Twan (Corresponding Author); Ludwig, Marie Gabrielle (Corresponding Author).

In: Biomaterials, Vol. 178, 01.09.2018, p. 481-495.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - Gauthier, Anne

AU - Fisch, Andreas

AU - Seuwen, Klaus

AU - Baumgarten, Birgit

AU - Ruffner, Heinz

AU - Aebi, Alexandra

AU - Rausch, Martin

AU - Kiessling, Fabian

AU - Bartneck, Matthias

AU - Weiskirchen, Ralf

AU - Tacke, Frank

AU - Storm, Gert

AU - Lammers, Twan

AU - Ludwig, Marie Gabrielle

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