Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.
Acetaldehyde Dehydrogenase Inhibitors
/ pharmacology
Animals
Anti-Inflammatory Agents
/ pharmacology
Biomimetic Materials
/ pharmacology
COVID-19
/ immunology
Colitis, Ulcerative
/ drug therapy
Disease Models, Animal
Disulfiram
/ pharmacokinetics
Drug Carriers
/ pharmacology
Humans
Immunosuppressive Agents
/ pharmacology
Lactoferrin
/ metabolism
Lipopolysaccharides
/ immunology
Macrophages
/ drug effects
Mice
Mice, Inbred C57BL
Nanoparticles
/ therapeutic use
Pyroptosis
/ drug effects
SARS-CoV-2
Systemic Inflammatory Response Syndrome
/ drug therapy
Treatment Outcome
COVID-19 Drug Treatment
disulfiram
inflammation
lactoferrin
macrophage-targeting delivery
pyroptosis
sepsis
ulcerative colitis
Journal
Acta pharmacologica Sinica
ISSN: 1745-7254
Titre abrégé: Acta Pharmacol Sin
Pays: United States
ID NLM: 100956087
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
received:
21
06
2021
accepted:
22
08
2021
pubmed:
26
9
2021
medline:
9
11
2021
entrez:
25
9
2021
Statut:
ppublish
Résumé
Sepsis is a dysregulated immune response to infection and potentially leads to life-threatening organ dysfunction, which is often seen in serious Covid-19 patients. Disulfiram (DSF), an old drug that has been used to treat alcohol addiction for decades, has recently been identified as a potent inhibitor of the gasdermin D (GSDMD)-induced pore formation that causes pyroptosis and inflammatory cytokine release. Therefore, DSF represents a promising therapeutic for the treatment of inflammatory disorders. Lactoferrin (LF) is a multifunctional glycoprotein with potent antibacterial and anti-inflammatory activities that acts by neutralizing circulating endotoxins and activating cellular responses. In addition, LF has been well exploited as a drug nanocarrier and targeting ligands. In this study, we developed a DSF-LF nanoparticulate system (DSF-LF NP) for combining the immunosuppressive activities of both DSF and LF. DSF-LF NPs could effectively block pyroptosis and inflammatory cytokine release from macrophages. Treatment with DSF-LF NPs showed remarkable therapeutic effects on lipopolysaccharide (LPS)-induced sepsis. In addition, this therapeutic strategy was also applied to treat ulcerative colitis (UC), and substantial treatment efficacy was achieved in a murine colitis model. The underlying mode of action of these DSF-LF-NPs may contribute to efficiently suppressing macrophage-mediated inflammatory responses and ameliorating the complications caused by sepsis and UC. As macrophage pyroptosis plays a pivotal role in inflammation, this safe and effective biomimetic nanomedicine may offer a versatile therapeutic strategy for treating various inflammatory diseases by repurposing DSF.
Identifiants
pubmed: 34561552
doi: 10.1038/s41401-021-00770-w
pii: 10.1038/s41401-021-00770-w
pmc: PMC8461433
doi:
Substances chimiques
Acetaldehyde Dehydrogenase Inhibitors
0
Anti-Inflammatory Agents
0
Drug Carriers
0
Immunosuppressive Agents
0
Lipopolysaccharides
0
Lactoferrin
EC 3.4.21.-
Disulfiram
TR3MLJ1UAI
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1913-1920Informations de copyright
© 2021. The Author(s), under exclusive licence to CPS and SIMM.
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