Nasal inhalation of antiviral microparticulate powders to target early infection of upper airways

During the COVID-19 pandemic, several compounds among which chloroquine diphosphate (CqP), have been repurposed as anti-SARS-CoV-2 drugs. Critically, studies were most often performed by systemic drug administration, whereas the early viral infection of human body appeared in the upper respiratory tract. This research addressed the delivery strategy for depositing a powder aerosol of CqP onto the upper airways by a nasal inhalation act. By formulating the drug as nasal microparticulate aerodynamic powder, the loco-regional application of particle aerosol concentrates the drug primarily on the upper airway epithelia where the virus replicates. Nasal microparticulate powders of CqP, with and without excipients, were engineered by spray drying, obtaining particle size, density and morphology suitable for aerosolization and deposition onto the upper respiratory tract. The powders were loaded into a pre-metered device for oral inhalation of dry powders that was innovatively actuated by a nasal sharp sniff. The generated nasal airflow, measured in healthy volunteers, enabled powder dose emission from the inhaler. Chloroquine diphosphate microparticles, deposited on rabbit nasal mucosa ex vivo, led in less than 45 min to CqP concentrations within the epithelial cells between 30-70 mM. The in vitro CqP concentrations inhibiting SARS-CoV-2 replication, were in the mu M range. The virus inhibition studied in Vero E6 cells was further enhanced when the cells were pre-treated with the drug powder before infection. In conclusion, the simple nasal sniff of an antiviral aerodynamic powder could be active against airborne viral early infection, limiting the exposition of the whole body to undesired drug effects.