人体鼻腔中药物气雾剂的吸收与清除：计算流体动力学模型的开发
Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.
作者信息
Rygg Alex, Longest P Worth
机构信息
1 Department of Mechanical and Nuclear Engineering, Virginia Commonwealth University , Richmond, Virginia.
2 Department of Pharmaceutics, Virginia Commonwealth University , Richmond, Virginia.
出版信息
J Aerosol Med Pulm Drug Deliv. 2016 Oct;29(5):416-431. doi: 10.1089/jamp.2015.1252. Epub 2016 Jan 29.
PURPOSE
The objective of this study was to develop a computational fluid dynamics (CFD) model to predict the deposition, dissolution, clearance, and absorption of pharmaceutical particles in the human nasal cavity.
METHODS
A three-dimensional nasal cavity geometry was converted to a surface-based model, providing an anatomically-accurate domain for the simulations. Particle deposition data from a commercial nasal spray product was mapped onto the surface model, and a mucus velocity field was calculated and validated with in vivo nasal clearance rates. A submodel for the dissolution of deposited particles was developed and validated based on comparisons to existing in vitro data for multiple pharmaceutical products. A parametric study was then performed to assess sensitivity of epithelial drug uptake to model conditions and assumptions.
RESULTS
The particle displacement distance (depth) in the mucus layer had a modest effect on overall drug absorption, while the mucociliary clearance rate was found to be primarily responsible for drug uptake over the timescale of nasal clearance for the corticosteroid mometasone furoate (MF). The model revealed that drug deposition in the nasal vestibule (NV) could slowly be transported into the main passage (MP) and then absorbed through connection of the liquid layer in the NV and MP regions. As a result, high intersubject variability in cumulative uptake was predicted, depending on the length of time the NV dose was left undisturbed without blowing or wiping the nose.
CONCLUSIONS
This study has developed, for the first time, a complete CFD model of nasal aerosol delivery from the point of spray formation through absorption at the respiratory epithelial surface. For the development and assessment of nasal aerosol products, this CFD-based in silico model provides a new option to complement existing in vitro nasal cast studies of deposition and in vivo imaging experiments of clearance.
目的
本研究的目的是开发一种计算流体动力学（CFD）模型，以预测药物颗粒在人体鼻腔中的沉积、溶解、清除和吸收情况。
方法
将三维鼻腔几何结构转换为基于表面的模型，为模拟提供解剖学上准确的区域。将来自商业鼻喷雾剂产品的颗粒沉积数据映射到表面模型上，并计算黏液速度场，并用体内鼻腔清除率进行验证。基于与多种药品现有体外数据的比较，开发并验证了沉积颗粒溶解的子模型。然后进行参数研究，以评估上皮药物摄取对模型条件和假设的敏感性。
结果
黏液层中颗粒的位移距离（深度）对总体药物吸收有适度影响，而对于皮质类固醇糠酸莫米松（MF），在鼻腔清除的时间尺度上，黏液纤毛清除率被发现是药物摄取的主要原因。该模型显示，鼻腔前庭（NV）中的药物沉积可缓慢转运至主通道（MP），然后通过NV和MP区域中液体层的连接被吸收。结果，预测了受试者间累积摄取的高度变异性，这取决于NV剂量在不擤鼻或擦鼻的情况下保持不受干扰的时间长度。
结论
本研究首次开发了一个完整的CFD模型，用于模拟从喷雾形成点到呼吸上皮表面吸收的鼻腔气雾剂递送过程。对于鼻腔气雾剂产品的开发和评估，这种基于CFD的计算机模拟模型提供了一种新的选择，以补充现有的关于沉积的体外鼻腔铸型研究和关于清除的体内成像实验。
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