Physicochemical Characteristics and In Vitro Toxicity/Anti-SARS-CoV-2 Activity of Favipiravir Solid Lipid Nanoparticles (SLNs)

Abstract

The rise of coronavirus (COVID-19) cases worldwide has driven the need to discover and develop novel therapeutics with superior efficacy to treat this disease. This study aims to develop an innovative aerosolized nano-formulation of favipiravir (FPV) as an anti-viral agent against coronavirus infection. The local delivery of FPV nanoparticles (NPs) via nebulization ensures that the drug can reach the site of infection, the lungs. Solid lipid NPs of favipiravir (FPV-SLNs) were formulated utilizing the hot-evaporation method. The physicochemical formulation properties were evaluated using dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The aerosol formulation performance was evaluated using an Andersen Cascade Impactor (ACI) at a flow rate of 15 L/min. The FPV-SLN formulation’s in vitro anti-viral activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was also evaluated using the SARS-CoV-2 pathogen (hCoV-19/Egypt/NRC-3/2020 isolate). The FPV-SLNs’ morphology was defined utilizing transmission electron microscopy, showing an irregular shape. By means of FPV-SLNs’ nebulization, a fine particle fraction of 60.2 ± 1.7% was produced with 60.2 ± 1.7%, and this finding suggests that FPV-SLNs were appropriate for inhalation drug delivery with a particle size of 537.6 ± 55.72 nm. Importantly, the FPV-SLNs showed anti-viral activity against SARS-CoV-2 with CC50 and IC50 values of 449.6 and 29.9 µg/mL, respectively. This study suggests that inhaled solid lipid NPs of favipiravir could potentially be used against coronavirus.

Use of Diaion HP20 Resin to Achieve High Rutin Containing Moringa oleifera Extract: Its Solubility and Anti-Bacterial Properties and Possible Applications in Nebulizer Formulation for COVID Patients

“…While some drugs readily dissolve in water, some require co-solvents such as ethanol or propylene glycol for solubilization. With the current observations of effective solubility and function of rutin-arginine mixture, it is tempting to speculate the possibility of development of a nebulizer solution of rutin and arginine in water in place of strategies of delivery of water-insoluble drugs, as liposomes (Tulbah & Lee, 2021). Highest hepatoprotective effects was seen in animals with hepatic injury due to oxidative stress by the co-administration of rutin and L-arginine (Acquaviva et al, 2009;Costa et al, 2014), hence use of arginine in the nebulizer formulation of rutin appears feasible.…”

In vitro evaluation of nebulized eucalyptol nano-emulsion formulation as a potential COVID-19 treatment

“…The concentration (IC50) of EUC-NE formulation necessary to decrease half of the SARS-CoV-2virus-induced cytopathic effect compared to the control cells (untreated) was measured ( Mostafa et al, 2020 ; A. S. Tulbah & Lee, 2021 ). Vero-E6 cells (2.4×10 4 cells) were prepared as described above and different concentrations of EUC-NE (7.81–125 µg/ml) were added and incubated for 72 h. The cells were then fixed with 100 µl of paraformaldehyde solution.…”

“…COVID-19, an acute respiratory infection caused by the SARS-CoV-2 virus ( Jiang et al, 2020 , Richardson et al, 2020 ; A. S. Tulbah & Lee, 2021 ), is currently one of the major cause of death worldwide ( Ciotti et al, 2020 ; A. Tulbah, 2021 ).…”

An overview on nanoparticle-based strategies to fight viral infections with a focus on COVID-19

“…Researchers produced a novel aerosolized SLNs-formulation of favipiravir (FPV) as an antiviral factor versus SARS-CoV-2. The results showed that FPV-SLNs were suitable for intranasal injection [ 70 ].…”