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.

FROM THE CLINICAL EDITOR:

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: Matthias Bartneck, Franziska Marie Peters, Klaudia Theresa Warzecha, Michaela Bienert, Louis van Bloois, Christian Trautwein, Twan Lammers, Frank Tacke
• Journal: Nanomedicine : nanotechnology, biology, and medicine (Nanomedicine) Vol. 10 Issue 6 Pg. 1209-20 (Aug 2014) ISSN: 1549-9642 [Electronic] United States
• PMID: 24607939 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Cytokines
• Liposomes
• Dexamethasone

Topics

• Anti-Inflammatory Agents (administration & dosage, pharmacology)
• Cell Movement
• Cells, Cultured
• Cytokines (immunology)
• Dexamethasone (administration & dosage, pharmacology)
• Humans
• Liposomes
• Macrophages (cytology, drug effects, immunology)