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成人鼻腔喷雾剂的区域沉积:一项广泛的计算研究。

Regional deposition of nasal sprays in adults: A wide ranging computational study.

作者信息

Kiaee Milad, Wachtel Herbert, Noga Michelle L, Martin Andrew R, Finlay Warren H

机构信息

Department of Mechanical Engineering, University of Alberta, Edmonton, Canada.

Boehringer Ingelheim, Ingelheim am Rhein, Germany.

出版信息

Int J Numer Method Biomed Eng. 2018 May;34(5):e2968. doi: 10.1002/cnm.2968. Epub 2018 Mar 25.

Abstract

The present work examines regional deposition within the nose for nasal sprays over a large and wide ranging parameter space by using numerical simulation. A set of 7 realistic adult nasal airway geometries was defined based on computed tomography images. Deposition in 6 regions of each nasal airway geometry (the vestibule, valve, anterior turbinate, posterior turbinate, olfactory, and nasopharynx) was determined for varying particle diameter, spray cone angle, spray release direction, particle injection speed, and particle injection location. Penetration of nasal spray particles through the airway geometries represented unintended lung exposure. Penetration was found to be relatively insensitive to injection velocity, but highly sensitive to particle size. Penetration remained at or above 30% for particles exceeding 10 μm in diameter for several airway geometries studied. Deposition in the turbinates, viewed as desirable for both local and systemic nasal drug delivery, was on average maximized for particles ranging from ~20 to 30 μm in diameter, and for low to zero injection velocity. Similar values of particle diameter and injection velocity were found to maximize deposition in the olfactory region, a potential target for nose-to-brain drug delivery. However, olfactory deposition was highly variable between airway geometries, with maximum olfactory deposition ranging over 2 orders of magnitude between geometries. This variability is an obstacle to overcome if consistent dosing between subjects is to be achieved for nose-to-brain drug delivery.

摘要

本研究通过数值模拟,在一个大范围的参数空间内考察了鼻腔喷雾剂在鼻腔内的区域沉积情况。基于计算机断层扫描图像定义了一组7种真实的成人鼻气道几何模型。针对不同的颗粒直径、喷雾锥角、喷雾释放方向、颗粒注入速度和颗粒注入位置,确定了每个鼻气道几何模型6个区域(前庭、瓣膜、前鼻甲、后鼻甲、嗅觉区和鼻咽)内的沉积情况。鼻腔喷雾颗粒穿过气道几何模型的穿透情况代表了意外的肺部暴露。研究发现,穿透情况对注入速度相对不敏感,但对颗粒大小高度敏感。对于所研究的几种气道几何模型,直径超过10μm的颗粒的穿透率保持在30%或以上。鼻甲内的沉积被认为对于局部和全身鼻腔给药都是理想的,对于直径约为20至30μm的颗粒以及低至零的注入速度,平均沉积量最大。发现类似的颗粒直径和注入速度值可使嗅觉区内的沉积最大化,嗅觉区是鼻脑给药的潜在靶点。然而,气道几何模型之间的嗅觉沉积差异很大,不同模型之间的最大嗅觉沉积范围超过2个数量级。如果要在受试者之间实现鼻脑给药的一致给药剂量,这种变异性是一个需要克服的障碍。

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