Comparison of Aerosol Deposition Between a Cynomolgus Macaque and a 3D Printed Cast Model of the Animal

• Published in: Pharmaceutical research 2023-03, Vol.40 (3), p.765-775
• Main Authors: Creppy, Justina, Cabrera, Maria, Kahlaoui, Nidhal, Pardessus, Jeoffrey, Lemaitre, Julien, Naninck, Thibaut, Delache, Benoît, Roseau, Georges, Ducancel, Frédéric, Vecellio, Laurent
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Aerosols; Animal experimentation; Animal models; Animal research; Animals; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Computed tomography; Health aspects; Humans; Lung; Macaca; Medical Law; Nebulizers and Vaporizers; Original; Original Research Article; Particle Size; Pharmacology/Toxicology; Pharmacy; Printing, Three-Dimensional; Respiratory tract; Statistical analysis
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-022-03466-w

Purpose Preclinical aerosol studies using animals are essential for evaluating toxic or therapeutic effects on human respiratory tract. Macaques are relevant animal models for respiratory studies, but they are sensitive, expensive and difficult-to-access. Methods In the context of preliminary studies before animal experiments, we set up an alternative in vitro anatomical model of macaque airways to reduce, refine and replace (3Rs) the animals. We printed an in vitro anatomical cast until the third bronchial division from X-ray computed tomography data of a healthy cynomolgus macaque. This in vitro model was then connected to a respiratory pump to mimic macaque’s breathing. We assessed the relevance of this in vitro model, by comparing aerosol deposition patterns obtained with the anatomical model and in three macaques using planar gamma camera imaging. DTPA- 99m Technetium aerosols were produced using three jet nebulizers, generating three different particle sizes: 13.1, 3.2 and 0.93 µm in terms of the mass median aerodynamic diameter (MMAD). Results The data showed no statistical differences between the animal and anatomical in vitro models in terms of total aerosol deposited in the airways. However, the distribution of the deposition in the airways showed a higher deposited fraction in the upper respiratory tract in the animals than the in vitro model for all particle sizes . Conclusions The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.