Delivery Device And Method For Aerosol Pathogen Exposure And Inhaled Therapeutic In A Macaque Model

Justina Creppy^1,2 , Benoit Delache¹, Maria Cabrera², Georges Roseau³, Cécile Herate¹, Thibaut Naninck¹, Asma Berriche¹, Quentin Sconosciuti¹, Eléana Navarre¹, Frederic Ducancel¹ & Laurent Vecellio^2,3

¹CEA/IDMIT, Fontenay aux Roses, France

² CEPR, INSERM U1100, University of Tours, Tours, France

³ PST-A, University of Tours, Tours, France

Summary

The main objective of this study was to develop an inhalation delivery device for macaque allowing either pathogen and drug administration. Using an inhalation device close to human device, it will allow rapid transfer to clinical trial and will give a high level of confidence if human study is not possible. Aerosol deposition measurement in 3 macaques have been performed by gamma camera using five different nebulizers with a face mask: one standard jet nebulizer with a 0.4µm MMAD, one standard jet nebulizer with a 3.2µm MMAD, one standard jet nebulizer with a 13.9µm MMAD, one prototype of jet nebulizer with 3.9µm MMAD and a second prototype using mesh nebulizer with a 3.9µm MMAD. Results show a decrease of aerosol deposition variability when using prototypes in comparison with standard jet nebulizer (34% and 30% respectively for prototype 1 and 2 vs 54%, 61%, 75% for standard nebulizers). Mesh nebulizer has the higher efficiency in terms of total airways deposition (37% vs 2.5% in terms of nebulizer charge) and lung targeting. PET-Scan measurement using prototype number 2 confirms its ability to target the whole macaque lung without external air contamination validating its operation in Biological Safety Level 3 (BSL 3).

Key Message

We developed a tool for precise and reproducible aerosol administration in macaques allowing studies for both aerosol pathogen exposure and drug delivery.  It should help the rapid technological transfer to clinical trial.