ABSTRACT
Remdesivir is the only clinically available antiviral drug for the treatment of COVID-19. However, its very limited aqueous solubility confines its therapeutic activity and the development of novel inhaled nano-based drug delivery systems of remdesivir for enhanced lung tissue targeting and efficacy is internationally pursued. In this work 2,2-bis(hydroxymethyl)propionic acid (bis-MPA) hyperbranched dendritic nano-scaffolds were employed as nanocarriers of remdesivir. The produced nano-formulations, empty and loaded, consisted of monodisperse nanoparticles with spherical morphology and neutral surface charge and sizes ranging between 80 and 230 nm. The entrapment efficiency and loading capacity of the loaded samples were 82.0% and 14.1%, respectively, whereas the release of the encapsulated drug was complete after 48 h. The toxicity assays in healthy MRC-5 lung diploid fibroblasts and NR8383 alveolar macrophages indicated their suitability as potential remdesivir carriers in the respiratory system. The novel nano-formulations are non-toxic in both tested cell lines, with IC50 values higher than 400 µΜ after 72 h treatment. Moreover, both free and encapsulated remdesivir exhibited very similar IC50 values, at the range of 80-90 µM, while its aqueous solubility was increased, overall presenting a suitable profile for application in inhaled delivery of therapeutics.
ABSTRACT
World Health Organization (WHO) has assessed that coronavirus disease 2019 (COVID-19) as an epidemic. However, an effective antiviral for COVID-19 is still uncertain. Since the onset of the outbreak, the scientific and clinical community keep proposing many agents that would have efficacy against COVID-19. Arbidol is an indole core with proven effectiveness against influenza over the past few years apart from critics. The concrete hypothesis of arbidol interaction with spike glycoprotein prevents the entry of virus. Further, demonstrated clinical efficiency of arbidol against RNA virus and broad-spectrum inhibition of influenza A and B virus, adenovirus, and other viruses, including hepatitis C virus, drives us to seek more understating of the molecule and its clinical possibilities. In this review, we attempt to describe the many possible hypotheses of arbidol against Covid-19.