Disulfiram-loaded lactoferrin nanoparticles for treating inflammatory diseases

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Immunology

Background:

• Sepsis is a life-threatening organ dysfunction due to dysregulated immune response to infection.
• Gasdermin D (GSDMD)-induced pyroptosis drives inflammation and cytokine release in sepsis and severe COVID-19.
• Disulfiram (DSF) inhibits GSDMD pore formation, and Lactoferrin (LF) has anti-inflammatory and antibacterial properties.

Purpose of the Study:

• To develop a Disulfiram-Lactoferrin nanoparticulate system (DSF-LF NP) for synergistic anti-inflammatory effects.
• To evaluate the therapeutic efficacy of DSF-LF NPs in preclinical models of sepsis and ulcerative colitis (UC).

Main Methods:

• Formulation of a Disulfiram-Lactoferrin nanoparticulate system (DSF-LF NP).
• Assessment of DSF-LF NP's ability to inhibit pyroptosis and inflammatory cytokine release in macrophages.
• In vivo testing of DSF-LF NPs in lipopolysaccharide (LPS)-induced sepsis and a murine colitis model.

Main Results:

• DSF-LF NPs effectively blocked pyroptosis and inflammatory cytokine release from macrophages.
• DSF-LF NP treatment demonstrated significant therapeutic effects in LPS-induced sepsis.
• Substantial treatment efficacy was observed in a murine model of ulcerative colitis.

Conclusions:

• The developed DSF-LF NP system offers a promising therapeutic strategy for inflammatory diseases.
• This biomimetic nanomedicine effectively suppresses macrophage-mediated inflammation.
• Repurposing Disulfiram via nanomedicine provides a versatile approach for treating sepsis, UC, and other inflammatory conditions.