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All Studies   Meta Analysis    Recent:   

Inhaled Ivermectin-Loaded Lipid Polymer Hybrid Nanoparticles: Development and Characterization

Kassaee et al., Pharmaceutics, doi:10.3390/pharmaceutics16081061
Aug 2024  
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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. * >10% efficacy, ≥3 studies.
4,800+ studies for 95 treatments. c19ivm.org
In Vitro study developing ivermectin-loaded lipid polymer hybrid nanoparticles (LPHNPs) as a potential dry powder inhalation formulation for pulmonary delivery.
68 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 H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Kassaee et al., 12 Aug 2024, peer-reviewed, 5 authors. Contact: nazrul.islam@qut.edu.au (corresponding author).
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Inhaled Ivermectin-Loaded Lipid Polymer Hybrid Nanoparticles: Development and Characterization
Seyedeh Negin Kassaee, Godwin A Ayoko, Derek Richard, Tony Wang, Nazrul Islam
Pharmaceutics, doi:10.3390/pharmaceutics16081061
Ivermectin (IVM), a drug originally used for treating parasitic infections, is being explored for its potential applications in cancer therapy. Despite the promising anti-cancer effects of IVM, its low water solubility limits its bioavailability and, consequently, its biological efficacy as an oral formulation. To overcome this challenge, our research focused on developing IVM-loaded lipid polymer hybrid nanoparticles (LPHNPs) designed for potential pulmonary administration. IVM-loaded LPHNPs were developed using the emulsion solvent evaporation method and characterized in terms of particle size, morphology, entrapment efficiency, and release pattern. Solid phase characterization was investigated by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated spherical-shaped particles between 302 and 350 nm. Developed formulations showed an entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within 96 h. Carr's index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper flowability of the fabricated LPHNPs. The in vitro aerosolization analysis revealed fine particle fractions (FPFs) ranging from 18.53% to 24.77%. This in vitro study demonstrates the potential of IVM-loaded LPHNPs as a delivery vehicle through the pulmonary route.
Conflicts of Interest: The authors have declared no conflicts of interest.
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IVM-loaded LPHNPs were developed using the emulsion solvent ' 'evaporation method and characterized in terms of particle size, morphology, entrapment ' 'efficiency, and release pattern. Solid phase characterization was investigated by Fourier ' 'transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and ' 'thermogravimetric analysis (TGA). Using a Twin stage impinger (TSI) attached to a device, ' 'aerosolization properties of the developed LPHNPs were studied at a flow rate of 60 L/min, ' 'and IVM was determined by a validated HPLC method. IVM-loaded LPHNPs demonstrated ' 'spherical-shaped particles between 302 and 350 nm. Developed formulations showed an ' 'entrapment efficiency between 68 and 80% and a sustained 50 to 60% IVM release pattern within ' '96 h. Carr’s index (CI), Hausner ratio (HR), and angle of repose (θ) indicated proper ' 'flowability of the fabricated LPHNPs. 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