Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.
Absorption and Clearance of Pharmaceutical Aerosols in the Human Nose: Development of a CFD Model.
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DOI：
10.1089/jamp.2015.1252
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发表时间：
2016-10
影响因子：
3.4
通讯作者：
Longest PW
中科院分区：
文献类型：
--
作者：
Rygg A;Longest PW
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、溶出、清除和吸收。将三维鼻腔几何形状转换为基于表面的模型，为模拟提供解剖学上精确的域。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，并计算粘液速度场，并用体内鼻清除率进行验证。基于与多种药品的现有体外数据的比较，开发并验证了沉积颗粒溶出的子模型。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。粘液层中的颗粒位移距离（深度）对总体药物吸收有适度的影响，而粘膜纤毛清除率被认为是主要负责药物吸收的皮质类固醇糠酸莫米松（MF）的鼻腔清除的时间尺度。该模型显示，药物沉积在鼻前庭（NV）可以缓慢地被转运到主通道（MP），然后通过NV和MP区域的液体层连接被吸收。因此，预测累积摄取的受试者间变异性较高，这取决于NV剂量未受干扰而不擤鼻涕或擦鼻涕的时间长度。本研究首次开发了一个完整的CFD模型，从喷雾形成到呼吸道上皮表面的吸收，描述了鼻内气雾剂的输送。对于鼻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，以补充现有的沉积体外鼻管型研究和清除体内成像实验。
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. 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. 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. 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.
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影响因子：
3.3
作者：
Hubal, EAC;Fedkiw, PS;Kimbell, JS
通讯作者：
Kimbell, JS
鼻内递送绕过靶向治疗剂到中枢神经系统并治疗神经退行性疾病的血脑屏障。
影响因子：
2.4
作者：
Hanson LR;Frey WH 2nd
通讯作者：
Frey WH 2nd
DOI：
10.1089/jamp.2009.0757
发表时间：
2010-06-01
影响因子：
3.4
作者：
Bur, Michael;Huwer, Hanno;Lehr, Claus-Michael
通讯作者：
Lehr, Claus-Michael
影响因子：
3.8
作者：
Bush, ML;Frederick, CB;Ultman, JS
通讯作者：
Ultman, JS
影响因子：
5.8
作者：
Buttini, Francesca;Miozzi, Michele;Forbes, Ben
通讯作者：
Forbes, Ben