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Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2

Eleraky et al., International Journal of Nanomedicine, doi:10.2147/IJN.S423251
Oct 2023  
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Curcumin for COVID-19
15th treatment shown to reduce risk in February 2021
*, now with p = 0.0000000096 from 27 studies.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments.
In Silico, In Vitro, and In Vivo study showing antiviral efficacy of a curcumin nanoformulation against SARS-CoV-2. Molecular docking revealed potential binding and inhibition of curcumin with viral proteins involved in entry and replication, including the main protease, RNA-dependent RNA polymerase (RdRp), and the receptor binding domain (RBD) of the spike protein. An optimized intranasal curcumin transferosome-loaded thermosensitive gel was formulated. This nanoformulation displayed strong anti-SARS-CoV-2 activity at low concentrations in Vero E6 cells with minimal cytotoxicity. After intranasal administration in rabbits, the nanoformulation showed 226% higher relative bioavailability and 2.5 times longer mean residence time compared to free curcumin gel, indicating improved lung delivery. Authors conclude the nanoformulation is a promising antiviral treatment for COVID-19.
45 preclinical studies support the efficacy of curcumin for COVID-19:
In Silico studies predict inhibition of SARS-CoV-2 with curcumin or metabolites via binding to the spikeA,5,10,12,18,21 (and specifically the receptor binding domainB,8,11,14), MproC,5,7,9-11,13,14,16,19,21,22,24,35, RNA-dependent RNA polymeraseD,11,20, ACE2E,12,13,15, nucleocapsidF,6,23, nsp10G,23, and helicaseH,25 proteins. In Vitro studies demonstrate inhibition of the spikeA,30 (and specifically the receptor binding domainB,38), MproC,17,30,35,37, ACE2E,38, and TMPRSS2I,38 proteins. In Vitro studies demonstrate efficacy in Calu-3J,36, A549K,30, 293TL,1, HEK293-hACE2M,17,28, 293T/hACE2/TMPRSS2N,29, Vero E6O,7,11,21,28,30-32,34,36, and SH-SY5YP,27 cells. Curcumin is predicted to inhibit the interaction between the SARS-CoV-2 spike protein receptor binding domain and the human ACE2 receptor for the delta and omicron variants8, decreases pro-inflammatory cytokines induced by SARS-CoV-2 in peripheral blood mononuclear cells34, and alleviates SARS-CoV-2 spike protein-induced mitochondrial membrane damage and oxidative stress1.
4 studies investigate novel formulations of curcumin for improved efficacy11,26,39,40
Eleraky et al., 16 Oct 2023, peer-reviewed, 7 authors. Contact:
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperCurcuminAll
Curcumin Transferosome-Loaded Thermosensitive Intranasal in situ Gel as Prospective Antiviral Therapy for SARS-Cov-2
Nermin E Eleraky, Mahmoud El-Badry, Mahmoud M Omar, Wesam M El-Koussi, Noha G Mohamed, Mohamed A Abdel-Lateef, Abeer S Hassan
International Journal of Nanomedicine, doi:10.2147/ijn.s423251
Purpose: Immunomodulatory and broad-spectrum antiviral activities have motivated the evaluation of curcumin for Coronavirus infection 2019 (COVID-19) management. Inadequate bioavailability is the main impediment to the therapeutic effects of oral Cur. This study aimed to develop an optimal curcumin transferosome-loaded thermosensitive in situ gel to improve its delivery to the lungs. Methods: Transferosomes were developed by using 3 3 screening layouts. The phospholipid concentration as well as the concentration and type of surfactant were considered independent variables. The entrapment efficiency (EE%), size, surface charge, and polydispersity index (PDI) were regarded as dependent factors. A cold technique was employed to develop thermosensitive in-situ gels. Optimized transferosomes were loaded onto the selected gels. The produced gel was assessed based on shape attributes, ex vivo permeability enhancement, and the safety of the nasal mucosa. The in vitro cytotoxicity, antiviral cytopathic effect, and plaque assay (CV/CPE/Plaque activity), and in vivo performance were evaluated after intranasal administration in experimental rabbits. Results: The optimized preparation displayed a particle size of 664.3 ± 69.3 nm, EE% of 82.8 ± 0.02%, ZP of -11.23 ± 2.5 mV, and PDI of 0.6 ± 0.03. The in vitro curcumin release from the optimized transferosomal gel was markedly improved compared with that of the free drug-loaded gel. An ex vivo permeation study revealed a significant improvement (2.58-fold) in drug permeability across nasal tissues of sheep. Histopathological screening confirmed the safety of these preparations. This formulation showed high antiviral activity against SARS-CoV-2 at reduced concentrations. High relative bioavailability (226.45%) was attained after the formula intranasally administered to rabbits compared to the free drug in-situ gel. The curcumin transferosome gel displayed a relatively high lung accumulation after intranasal administration. Conclusion: This study provides a promising formulation for the antiviral treatment of COVID-19 patients, which can be evaluated further in preclinical and clinical studies.
Author Contributions All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work. Disclosure The authors declare that they have no known competing financial interests or personal relationships that could influence the work reported in this study.
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