Fluorescent cell-traceable dexamethasone-loaded liposomes for the treatment of inflammatory liver diseases
Open accessAbstract
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.
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Dexamethasone-loaded nanoparticles reprogram macrophages towards a more anti-inflammatory and restorative phenotype in vitro, and reduce activation of HSCs and collagen deposition in a chronic liver injury mouse model.
“For example, dexamethasone-loaded nanoparticles have shown to reprogram macrophages towards a more anti-inflammatory and restorative phenotype in vitro, and reduced activation of HSCs and collagen deposition in a chronic liver injury mouse model (160).”
From Targeting macrophages in liver fibrosis (2026) · cites this paper as [160]
Section 3.3 reports that dexamethasone-loaded liposomes reduced hepatic stellate cell activation and collagen accumulation in mice with chronic liver injury. The Introduction reports reduced inflammatory functions of macrophages in vitro, and the Macrophage polarization discussion reports anti-inflammatory M2 differentiation, but the paper does not establish a restorative macrophage phenotype in vitro. (LLM, conf=0.84)
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- Authors
- Bartneck, M., Scheyda, K. M., Warzecha, K. T., Rizzo, L. Y., Hittatiya, K., Luedde, T., Storm, G., Trautwein, C., Lammers, T., & Tacke, F.
- Affiliations
- RWTH Aachen University (DE)
- University of Bonn (DE)
- Utrecht University (NL)
- Corresponding author
- Tacke, Frank
- Venue
- Biomaterials
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 37
- Pages
- 367-382
- ISSN
- 0142-9612 (ISSN-L)
- OpenAlex
- W1981491728
- Cited by
- 141
- References
- 35
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 8 · 2023: 13 · 2022: 13 · 2021: 27 · 2020: 14 · 2019: 11 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 4 · 2014: 1 · 2013: 1
- FWCI
- 3.41
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Biomaterials (publishedVersion)
- PubMed (publishedVersion)
- University of Twente Research Information (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- RWTH Publications (RWTH Aachen) (submittedVersion)
- University of Twente Research Information (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- RWTH Aachen
- German Research Foundation (DFG SFB/TRR 57)
- European Research Council (309495)
- Interdisciplinary Center for Clinical Research (IZKF)
- Topics
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- liposomal drug delivery, inflammatory liver disease, immune-mediated hepatitis, T cell depletion, liver fibrosis, acute liver injury, anti-inflammatory therapy
- MeSH terms
- Animals, Cell Survival, Dexamethasone, Fluorescence, Hepatitis, Immunosuppression Therapy, Inflammation, Liposomes, Liver, Liver Cirrhosis, Liver Diseases, Mice, Inbred C57BL, Organ Specificity, T-Lymphocytes, Tissue Distribution, Cell Death, Immunomodulation
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