Simultaneous nasal and lung delivery of an antiviral metallodrug using a dual targeting powder formulation
Han Cong Seow1, Suyu Wang2, Hongzhe Sun2 & Jenny K.W. Lam1,3
1Department of Pharmacology and Pharmacy, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong SAR
2Department of Chemistry, State Key Laboratory of Synthetic Chemistry, CAS-HKU Joint Laboratory of Metallomics on Health and Environment, The University of Hong Kong, Pokfulam, Hong Kong SAR
3Department of Pharmaceutics, UCL School of Pharmacy, University College London, UK
Summary
In the fight against respiratory viral infections, new aerosol drug delivery strategies are developed to target the entire respiratory tract. As highly contagious and deadly viruses infect both the upper and lower respiratory tract, an antiviral therapy that can deliver to the target sites would be most effective. This study aimed to reformulate ranitidine bismuth citrate (RBC), an anti-ulcer drug with broad-spectrum coronavirus activity, as a dual particle size powder formulation that targets both the nasal cavity and deep lung by a single route of intranasal administration. Spray freeze drying (SFD) using appropriate atomising nozzles produces distinctly large (>10 μm) and small (<5 μm) particles for nasal and lung deposition, respectively. When dispersed from a nasal device, the aerosol performance of the powder was evaluated using the Next Generation Impactor (NGI) coupled with a glass expansion chamber. By blending two formulations with different particle sizes, a single powder formulation with bimodal size distribution and dual aerosol deposition characteristics 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 a lower dose of SFD powder to mice resulted in significantly higher drug concentration in the lungs. Overall, a dual targeting powder formulation of RBC with customisable nasal and lung deposition profile was developed. This innovative formulation strategy may potentially be applied to deliver therapeutic agents to the human airways for respiratory diseases.
Key Message
Dual targeting powder formulation of repurposed ranitidine bismuth citrate (RBC) demonstrates a new drug delivery platform for antiviral agents in the treatment and prevention of respiratory viral infections.