In response to the COVID-19 pandemic threats caused by emerging respiratory viral infection, a safe and efficient broad-spectrum antiviral therapy at early onset of infection can significantly lead to a better therapeutic outcome. Novel aerosol drug delivery strategies are developed to target the entire respiratory tract as highly contagious viruses infect both the upper and lower respiratory tract. Ranitidine bismuth citrate (RBC) and bismuth containing drugs, with broad-spectrum coronavirus activity, are reformulated as dual particle size powder formulations that target both the nasal cavity and deep lung by a single route of intranasal administration1. Spray freeze drying (SFD) using appropriate atomizing nozzles produces distinctly large (>10 μm) and small (<5 μm) particles for nasal and lung deposition, respectively. By blending two formulations with different particle sizes, a single powder formulation with bimodal size distribution and dual aerosol deposition characteristic was produced. The aerosol deposition profile can potentially be manipulated by varying the powder mixing ratio. Compared to orally administered unformulated RBC, intratracheal administration of 40 times lower dose of RBC SFD powder to mice resulted in significantly higher drug concentration in the lungs. Overall, a dual targeting powder formulation of metallodrug RBC with customizable nasal and lung deposition profile was developed. This innovative metallodrug formulation may potentially be applied to fight against broad-spectrum virus-related respiratory diseases. 

Figure 1. (Upper Left) Volumetric particle size distribution and (Bottom Left) aerosol performance of different RBC powder formulations. 

We thank the Research Grants Council (R7070-18, 17308921, 2122-7S04), ITF (ITS/278/20) and The University of Hong Kong (Norman & Celia Yip Foundation and URC) for financial support. 

(1) Wang, R.; Chan, J. F.-W.; Wang, S.; Li, H.; Yuen, K.-Y.; Yuan, S.; Sun, H. et al. Chem Sci 2022, 13 (8), 2238-2248.