ABSTRACT
Coronavirus is a type of acute atypical respiratory disease representing the leading cause of death worldwide. Eucalyptol (EUC) known also as 1,8-cineole is a potential inhibitor candidate for COVID-19 (main protease-Mpro) with effective antiviral properties but undergoes physico-chemical instability and poor water solubility. Nano-emulsion (NE) is a promising drug delivery system to improve the stability and efficacy of drugs. This work focuses on studying the anti- COVID-19 activity of EUC by developing nebulized eucalyptol nano-emulsion (EUC-NE) as a potentially effective treatment for COVID-19. The EUC -NE formulation was prepared using Tween 80 as a surfactant. In vitro evaluation of the EUC-NE formulation displayed an entrapment efficiency of 77.49%, a droplet size of 122.37 nm, and an EUC % release of 84.7%. The aerodynamic characterization and cytotoxicity of EUC-NE formulation were assessed, and results showed high lung deposition and low inhibitory concentration. The antiviral mechanism of the EUC-NE formulation was performed, and it was found that it exerts its action by virucidal, viral replication, and viral adsorption. Our results confirmed the antiviral activity of the EUC-NE formulation against COVID-19 and the efficacy of nano-emulsion as a delivery system, which can improve the cytotoxicity and inhibitory activity of EUC.
ABSTRACT
Since December 2019, a pandemic of COVID-19 disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has rapidly spread across the globe. At present, the Food and Drug Administration (FDA) has issued emergency approval for the use of some antiviral drugs. However, these drugs still have limitations in the specific treatment of COVID-19, and as such, new treatment strategies urgently need to be developed. RNA-interference-based gene therapy provides a tractable target for antiviral treatment. Ensuring cell-specific targeted delivery is important to the success of gene therapy. The use of nanoparticles (NPs) as carriers for the delivery of small interfering RNA (siRNAs) to specific tissues or organs of the human body could play a crucial role in the specific therapy of severe respiratory infections, such as COVID-19. In this review, we describe a variety of novel nanocarriers, such as lipid NPs, star polymer NPs, and glycogen NPs, and summarize the pre-clinical/clinical progress of these nanoparticle platforms in siRNA delivery. We also discuss the application of various NP-capsulated siRNA as therapeutics for SARS-CoV-2 infection, the challenges with targeting these therapeutics to local delivery in the lung, and various inhalation devices used for therapeutic administration. We also discuss currently available animal models that are used for preclinical assessment of RNA-interference-based gene therapy. Advances in this field have the potential for antiviral treatments of COVID-19 disease and could be adapted to treat a range of respiratory diseases.