Center for Immunology of Viral, Autoimmune, Haematological and Bacterial Diseases (IMVA-HB/IDMIT), Université Paris-Saclay, Inserm, CEA, 18, Route du Panorama, DRF/JACOB/IDMIT, BAT 62 - Pce 308, 92265, Fontenay-Aux-Roses, Cedex, France.
Université de Tours, Centre d'Étude Des Pathologies Respiratoires, INSERM U1100, Tours, France.
Pharm Res. 2023 Mar;40(3):765-775. doi: 10.1007/s11095-022-03466-w. Epub 2023 Jan 18.
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.
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-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).
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.
The anatomical printed model appears to be a relevant in vitro tool to predict total aerosol deposition in macaque airways.
使用动物进行临床前气溶胶研究对于评估人类呼吸道的毒性或治疗效果至关重要。猕猴是呼吸研究的相关动物模型，但它们敏感、昂贵且难以获得。
在动物实验前的初步研究中，我们建立了一种替代的猕猴气道体外解剖模型，以减少、优化和替代（3R）动物。我们根据健康食蟹猴的 X 射线计算机断层扫描数据打印了一个体外解剖模型，直到第三支气管分支。然后，将该体外模型与呼吸泵连接，以模拟猕猴的呼吸。我们通过使用平面伽马相机成像，比较了在三个猕猴和解剖模型中获得的气溶胶沉积模式，评估了该体外模型的相关性。使用三个射流雾化器产生 DTPA-锝气溶胶，生成三种不同的粒径：质量中值空气动力学直径（MMAD）分别为 13.1、3.2 和 0.93µm。
在总气溶胶在气道中的沉积方面，动物和体外解剖模型之间的数据没有统计学差异。然而，对于所有粒径，动物模型的气道沉积分布显示在上呼吸道的沉积分数高于体外模型。
打印的解剖模型似乎是一种预测猕猴气道中总气溶胶沉积的相关体外工具。
