Delivery Device And Method For Aerosol Pathogen Exposure And Inhaled Therapeutic In A Macaque Model
Justina Creppy1,2 , Benoit Delache1, Maria Cabrera2, Georges Roseau3, Cécile Herate1, Thibaut Naninck1, Asma Berriche1, Quentin Sconosciuti1, Eléana Navarre1, Frederic Ducancel1 & Laurent Vecellio2,3
1CEA/IDMIT, Fontenay aux Roses, France
2 CEPR, INSERM U1100, University of Tours, Tours, France
3 PST-A, University of Tours, Tours, France
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).
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.