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Review
. 2023 Mar 22:14:1147991.
doi: 10.3389/fimmu.2023.1147991. eCollection 2023.

Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review

Aleksandra Zielińska  1 , Piotr Eder  2 , Jacek Karczewski  3 , Marlena Szalata  4 , Szymon Hryhorowicz  1 , Karolina Wielgus  5 , Milena Szalata  6 , Agnieszka Dobrowolska  2 , Atanas G Atanasov  7   8   9 , Ryszard Słomski  1 , Eliana B Souto  10   11
Affiliations
Review

Tocilizumab-coated solid lipid nanoparticles loaded with cannabidiol as a novel drug delivery strategy for treating COVID-19: A review

Aleksandra Zielińska et al. Front Immunol. .

Abstract

Commonly used clinical strategies against coronavirus disease 19 (COVID-19), including the potential role of monoclonal antibodies for site-specific targeted drug delivery, are discussed here. Solid lipid nanoparticles (SLN) tailored with tocilizumab (TCZ) and loading cannabidiol (CBD) are proposed for the treatment of COVID-19 by oral route. TCZ, as a humanized IgG1 monoclonal antibody and an interleukin-6 (IL-6) receptor agonist, can attenuate cytokine storm in patients infected with SARS-CoV-2. CBD (an anti-inflammatory cannabinoid and TCZ agonist) alleviates anxiety, schizophrenia, and depression. CBD, obtained from Cannabis sativa L., is known to modulate gene expression and inflammation and also shows anti-cancer and anti-inflammatory properties. It has also been recognized to modulate angiotensin-converting enzyme II (ACE2) expression in SARS-CoV-2 target tissues. It has already been proven that immunosuppressive drugs targeting the IL-6 receptor may ameliorate lethal inflammatory responses in COVID-19 patients. TCZ, as an immunosuppressive drug, is mainly used to treat rheumatoid arthritis, although several attempts have been made to use it in the active hyperinflammatory phase of COVID-19, with promising outcomes. TCZ is currently administered intravenously. It this review, we discuss the potential advances on the use of SLN for oral administration of TCZ-tailored CBD-loaded SLN, as an innovative platform for managing SARS-CoV-2 and related infections.

Keywords: COVID-19; cannabidiol (CBD); cytokine storm; oral drug therapy; solid lipid nanoparticles (SLN); tocilizumab (TCZ).

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Phases of the clinical course of COVID-19. Own drawing, based on (60).
Figure 2
Figure 2
Viral genome of SARS-CoV-2. Own drawing, based on (66).
Figure 3
Figure 3
Structure of tocilizumab [own drawing].
Figure 4
Figure 4
SARS-CoV-2 infection (left) and inhibition of intracellular signaling in cells by TCZ, resulting express of gp130 (right) [own drawing]. (1) Virus entry and infection of pneumocytes expressing the ACE2 receptor, recruiting antigen-presenting cells (dendritic cells and macrophages) into the lungs; (2) Activation of the NLRC4 inflammasome, which causes the overproduction of IL1β and IL 18, and causes the secretion of IL6 and ferritin by macrophages; (3) Upregulation resulting in cytokine release syndrome and macrophage recruitment to the lungs, contributing to ARDS.
Figure 5
Figure 5
Graphical summary of the influence on COVID-19 treatment of tocilizumab-coated solid lipid nanoparticles [own drawing].
Figure 6
Figure 6
Types of solid lipid nanoparticles. Own drawing based on (206).
See this image and copyright information in PMC

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