Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance
et al., Pharmaceutics, doi:10.3390/pharmaceutics17091101, Aug 2025
Ivermectin for COVID-19
4th treatment shown to reduce risk in
August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,500+ studies for
210+ treatments. c19early.org
|
In vitro study showing that poloxamer 407 (P407)-based solid dispersions of ivermectin significantly improve aqueous solubility, dissolution, and drug release compared to pure ivermectin.
76 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 H7N773, Dengue38,74,75 , HIV-175, Simian virus 4076, Zika38,77,78 , West Nile78, Yellow Fever79,80, Japanese encephalitis79, Chikungunya80, Semliki Forest virus80, Human papillomavirus58, Epstein-Barr58, BK Polyomavirus81, and Sindbis virus80.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins73,75,76,82 , shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing39, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination42,83, shows dose-dependent inhibition of wildtype and omicron variants37, exhibits dose-dependent inhibition of lung injury63,68, may inhibit SARS-CoV-2 via IMPase inhibition38, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation10, inhibits SARS-CoV-2 3CLpro55, may inhibit SARS-CoV-2 RdRp activity1,29, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages62, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation84, may interfere with SARS-CoV-2's immune evasion via ORF8 binding5, may inhibit SARS-CoV-2 by disrupting CD147 interaction85-88, may inhibit SARS-CoV-2 attachment to lipid rafts via spike NTD binding3, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1960,89, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage9, significantly mitigates bleomycin-induced pulmonary fibrosis by reducing collagen accumulation and inflammatory cell infiltration61, improves oxidative stress markers while suppressing myofibroblast proliferation61, may minimize SARS-CoV-2 induced cardiac damage41,49, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation90, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses2, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways36, increases Bifidobacteria which play a key role in the immune system91, has immunomodulatory52 and anti-inflammatory72,92 properties, and has an extensive and very positive safety profile93.
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Mezzano et al., 23 Aug 2025, Argentina, peer-reviewed, 5 authors.
Contact: cgarnero@unc.edu.ar (corresponding author), belen.mezzano@unc.edu.ar, soledad.bueno@unc.edu.ar, mrlonghi@unc.edu.ar, vfuertes@unc.edu.ar.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Abstract:
Article
Poloxamer-Based Biomaterial as a Pharmaceutical Strategy to Improve the Ivermectin Performance
, Maria Soledad Bueno 1
, Valeria Cintia Fuertes
, Marcela Raquel Longhi 1
- 1 Departamento de Ciencias Farmacéuticas, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Unidad de Investigación y Desarrollo en Tecnología Farmacéutica (UNITEFA) CONICET-UNC, Córdoba X5000HUA, Argentina; belen.mezzano@unc.edu.ar (B.A.M.); soledad.bueno@unc.edu.ar (M.S.B.); mrlonghi@unc.edu.ar (M.R.L.)
- 2 Departamento de Fisicoquímica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Instituto de Investigaciones en Fisicoquímica de Córdoba (INFIQC) CONICET-UNC, Córdoba X5000HUA, Argentina; vfuertes@unc.edu.ar
* Correspondence: cgarnero@unc.edu.ar
Abstract
Background: Poloxamers are promising biomaterials for drug delivery applications due to their ability to enhance biopharmaceutical properties. Methods: This study focused on designing solid dispersions of ivermectin using poloxamer 407 by the fusion method and evaluating how variables of synthesis affect the polymer's behavior and the resulting biopharmaceutical properties of ivermectin. Poloxamer 407 was selected based on a solubility test of preformulation studies. Initially, eight formulations were developed using different synthesis conditions, including polymer proportion, cooling gradient, and final process temperature. These were assessed by several characterization studies. Finally, saturation solubility dissolution profiles and in vitro drug release were also evaluated. Results: Acombination of techniques confirmed the compatibility between poloxamer 407 and ivermectin in the solid dispersions. The rate of temperature in the cooling process of synthesis showed a significant impact on the polymer self-assembly, affecting their ability to entrap ivermectin. The optimized solid dispersion comprised ivermectin and poloxamer 407 in a 1:1 w / w ratio prepared by rapid cooling. This decrease in the crystallinity index and the nanometric size of particles of the solid dispersions could explain their ability to improve 1600-fold the aqueous solubility, as well as enhance the drug dissolution and in vitro drug release compared to pure ivermectin. Conclusions: Therefore, it follows that these poloxamer-based solid dispersions are promising alternatives to improve the bioavailability of ivermectin.
Keywords: polymer; solid dispersion; fusion method; solubility; dissolution; crystallinity
DOI record:
{
"DOI": "10.3390/pharmaceutics17091101",
"ISSN": [
"1999-4923"
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"URL": "http://dx.doi.org/10.3390/pharmaceutics17091101",
"abstract": "<jats:p>Background: Poloxamers are promising biomaterials for drug delivery applications due to their ability to enhance biopharmaceutical properties. Methods: This study focused on designing solid dispersions of ivermectin using poloxamer 407 by the fusion method and evaluating how variables of synthesis affect the polymer’s behavior and the resulting biopharmaceutical properties of ivermectin. Poloxamer 407 was selected based on a solubility test of preformulation studies. Initially, eight formulations were developed using different synthesis conditions, including polymer proportion, cooling gradient, and final process temperature. These were assessed by several characterization studies. Finally, saturation solubility dissolution profiles and in vitro drug release were also evaluated. Results: A combination of techniques confirmed the compatibility between poloxamer 407 and ivermectin in the solid dispersions. The rate of temperature in the cooling process of synthesis showed a significant impact on the polymer self-assembly, affecting their ability to entrap ivermectin. The optimized solid dispersion comprised ivermectin and poloxamer 407 in a 1:1 w/w ratio prepared by rapid cooling. This decrease in the crystallinity index and the nanometric size of particles of the solid dispersions could explain their ability to improve 1600-fold the aqueous solubility, as well as enhance the drug dissolution and in vitro drug release compared to pure ivermectin. Conclusions: Therefore, it follows that these poloxamer-based solid dispersions are promising alternatives to improve the bioavailability of ivermectin.</jats:p>",
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