Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases.
Acta Pharmacol Sin
; 42(11): 1913-1920, 2021 11.
Article
in English
| MEDLINE | ID: covidwho-1437673
ABSTRACT
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Colitis, Ulcerative
/
Systemic Inflammatory Response Syndrome
/
Disulfiram
/
COVID-19
/
COVID-19 Drug Treatment
/
Lactoferrin
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Acta Pharmacol Sin
Journal subject:
Pharmacology
Year:
2021
Document Type:
Article
Affiliation country:
S41401-021-00770-w
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