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. 2023 Mar 27:18:1561-1575.
doi: 10.2147/IJN.S391462. eCollection 2023.

Antiviral Lipid Nanocarrier Loaded with Remdesivir Effective Against SARS-CoV-2 in vitro Model

Woo-Jin Jeon #  1 , Hong-Ki Lee #  2   3 , Young-Guk Na  1 , Minwoo Jung  1 , Su-Cheol Han  2 , Jeong Ho Hwang  2 , Eunhye Jung  4 , Dasom Hwang  4 , Jin Soo Shin  4 , Cheong-Weon Cho  1
Affiliations

Antiviral Lipid Nanocarrier Loaded with Remdesivir Effective Against SARS-CoV-2 in vitro Model

Woo-Jin Jeon et al. Int J Nanomedicine. .

Abstract

Introduction: The ongoing SARS-CoV-2 pandemic has affected public health, the economy, and society. This study reported a nanotechnology-based strategy to enhance the antiviral efficacy of the antiviral agent remdesivir (RDS).

Results: We developed a nanosized spherical RDS-NLC in which the RDS was encapsulated in an amorphous form. The RDS-NLC significantly potentiated the antiviral efficacy of RDS against SARS-CoV-2 and its variants (alpha, beta, and delta). Our study revealed that NLC technology improved the antiviral effect of RDS against SARS-CoV-2 by enhancing the cellular uptake of RDS and reducing SARS-CoV-2 entry in cells. These improvements resulted in a 211% increase in the bioavailability of RDS.

Conclusion: Thus, the application of NLC against SARS-CoV-2 may be a beneficial strategy to improve the antiviral effects of antiviral agents.

Keywords: SARS-CoV-2; antiviral effect; nanostructured lipid carrier; remdesivir; virus entry.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study.

Figures

Figure 1
Figure 1
Physicochemical properties of RDS-NLC. (a) Size and particle size distribution and (b) Transmission electron microscope images of RDS-NLC. (c) Particle size and zeta potential of Blank-NLC and RDS-NLC.
Figure 2
Figure 2
Physicochemical properties of RDS-NLC. (a) Differential scanning calorimetry (DSC) thermogram. (b) X-ray diffraction (XRD) pattern. (c) Fourier transform-infrared spectroscopy (FT-IR) of RDS, physical mixture, glycerol monostearate (GMS,) Myrj52, Blank-NLC, and RDS-NLC.
Figure 3
Figure 3
In vitro release profiles of RDS and RDS-NLC. (a) Cumulative release of RDS from RDS and RDS-NLC in PBS containing 2 w/v% SLS (pH 7.4). (b–f) Release kinetic model fitness of RDS and RDS-NLC using zero-order, first-order, Higuchi-, Hixson-Crowell, and Korsmeyer-Peppas models.
Figure 4
Figure 4
Antiviral effects of RDS and RDS-NLC against SARS-CoV-2 and variants. (a) Antiviral effect of RDS and RDS-NLC in SARS-CoV-2 infected Vero cells. (b) Comparison of plaque titer between various concentrations of RDS and RDS-NLC. (c) Quantification of viral RNA (S-protein) after treatment with various concentrations of RDS or RDS-NLC. (d-f) Antiviral effects of RDS and RDS-NLC in SARS-CoV-2 alpha-, beta-, and delta-variants. Data are presented as mean ± SD. **P < 0.01 versus control. ***P < 0.005 versus control. ****P < 0.0001 versus control. Conc., concentration; RDS, remdesivir.
Figure 5
Figure 5
Cellular uptake of RDS-NLC. (a) Fluorescent images of RDS-NLC (C6 labeled RDS-NLC, green signal) in Vero cells after 24 h of treatment. (b) Flow cytometry histograms of C6 solution (red) and RDS-NLC (green). Cells were incubated for 24 h. (c) Normalized amount of RDS metabolite (GS-441524) after treatments with RDS or RDS-NLC in Vero cells. (d) Immunofluorescent images of C6 labeled RDS-NLC in SARS-CoV-2 infected Vero cells. (e) Viral titer after treatment with RDS or RDS-NLC at different time points [pre-treatment (−2 h), co-treatment (0 h), and post-treatment (2 h)] in SARS-CoV-2 infected Vero cells. Data are presented as mean ± SD. *P < 0.05. **P < 0.01. ***P < 0.005.
Figure 6
Figure 6
Plasma concentration of GS-441524 after the injection of RDS (circle) and RDS-NLC (square) injections (10 mg/kg) in rats.
See this image and copyright information in PMC

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