Nanomedicine formulations for respiratory infections by inhalation delivery: Covid-19 and beyond

For respiratory infections treatment and prevention, we analyze for the first time the possibility of providing a broad range medication based on metallic nanoparticles colloids (NpC) delivery by controlled aerosol inhalation. (i) Based on in-vitro data combined with aerosol deposition characteristics in the respiratory system, we calculate the required effective formulations, dosages and delivery parameters for an aerosol inhalation treatment. The goal is to achieve an effective NpC inhibitory concentration (IC) in the target airway surface liquid (ASL); (ii) We evaluate the clinical safety of such dosages, drawing on information from animal testing data and regulatory limits in the USA for such nanoparticles aerosol inhalation safety. Our analysis indicates a wide range of potentially safe and effective dosages that can be clinically explored, targeting the upper respiratory and bronchial tree system. Similar dosages can also provide antibacterial effectiveness for prophylactic treatment in hospital intensive care units to lower the risk of ventilator-associated pneumonia (VAP). Our calculations are phenomenological, independent of mechanisms. Nevertheless, we highlight a mechanism of action by which any suitably designed NpC, with nanoparticles sized 2–10 nm and having a large negative zeta-potential, preferentially bind to viruses with predominantly positively-charged spike proteins. These will be ineffective against viruses with predominantly negatively-charged spike proteins. Accordingly, the popular silver metal base for NpC serves just as a construction ingredient, and other metal or metal-oxides which can serve to construct the noted nanoparticle properties would be similarly effective. We suggest that inhalation delivery of the proposed antiviral formulations could be applied as a first-line intervention while respiratory infections are primarily localized to the upper respiratory system and bronchial tree.