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Inhalable spray-dried dry powders combining ivermectin and niclosamide to inhibit SARS-CoV-2 infection in vitro

Su et al., International Journal of Pharmaceutics, doi:10.1016/j.ijpharm.2025.125302
Jan 2025  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments.
5,300+ studies for 115 treatments. c19ivm.org
In Vitro study showing that inhalable spray-dried dry powders combining ivermectin and niclosamide exhibit enhanced anti-SARS-CoV-2 activity compared to the individual drugs. Authors developed stable, amorphous powders with aerodynamic properties (1–5 μm particle size; emitted dose of 68–83% and fine particle fraction of 50–74%) ideal for direct lung delivery. The optimized combined formulation demonstrated an EC50 of 2.67 μM and an improved cytotoxic profile (CC50 of 45.99 μM) versus the individual treatments. Direct pulmonary delivery can improve local drug concentrations while minimizing systemic toxicity.
72 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N769, Dengue35,70,71, HIV-171, Simian virus 4072, Zika35,73,74, West Nile74, Yellow Fever75,76, Japanese encephalitis75, Chikungunya76, Semliki Forest virus76, Human papillomavirus55, Epstein-Barr55, BK Polyomavirus77, and Sindbis virus76.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins69,71,72,78, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing36, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination39,79, shows dose-dependent inhibition of wildtype and omicron variants34, exhibits dose-dependent inhibition of lung injury59,64, may inhibit SARS-CoV-2 via IMPase inhibition35, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation8, inhibits SARS-CoV-2 3CLpro52, may inhibit SARS-CoV-2 RdRp activity27, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages58, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation80, may interfere with SARS-CoV-2's immune evasion via ORF8 binding3, may inhibit SARS-CoV-2 by disrupting CD147 interaction81-84, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1957,85, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage7, may minimize SARS-CoV-2 induced cardiac damage38,46, increases Bifidobacteria which play a key role in the immune system86, has immunomodulatory49 and anti-inflammatory68,87 properties, and has an extensive and very positive safety profile88.
Su et al., 30 Jan 2025, peer-reviewed, 7 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
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