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脉动双向气溶胶流对鼻内嗅觉区域气溶胶输送的影响：一项针对个体患者的计算研究。

Pulsatile Bi-Directional Aerosol Flow Affects Aerosol Delivery to the Intranasal Olfactory Region: A Patient-Specific Computational Study.

作者信息

Farnoud Ali, Tofighian Hesam, Baumann Ingo, Martin Andrew R, Rashidi Mohammad M, Menden Micheal P, Schmid Otmar

机构信息

Institute of Computational Biology, Helmholtz Zentrum München, Munich, Germany.

Comprehensive Pneumology Center, Member of the German Center for Lung Research, Munich, Germany.

出版信息

Front Pharmacol. 2021 Nov 23;12:746420. doi: 10.3389/fphar.2021.746420. eCollection 2021.

DOI:10.3389/fphar.2021.746420
PMID:34887754
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8650014/
Abstract

The nasal olfactory region is a potential route for non-invasive delivery of drugs directly from the nasal epithelium to the brain, bypassing the often impermeable blood-brain barrier. However, efficient aerosol delivery to the olfactory region is challenging due to its location in the nose. Here we explore aerosol delivery with bi-directional pulsatile flow conditions for targeted drug delivery to the olfactory region using a computational fluid dynamics (CFD) model on the patient-specific nasal geometry. Aerosols with aerodynamic diameter of 1 µm, which is large enough for delivery of large enough drug doses and yet potentially small enough for non-inertial aerosol deposition due to, e.g., particle diffusion and flow oscillations, is inhaled for 1.98 s through one nostril and exhaled through the other one. The bi-directional aerosol delivery with steady flow rate of 4 L/min results in deposition efficiencies (DEs) of 50.9 and 0.48% in the nasal cavity and olfactory region, respectively. Pulsatile flow with average flow rate of 4 L/min (frequency: 45 Hz) reduces these values to 34.4 and 0.12%, respectively, and it mitigates the non-uniformity of right-left deposition in both the cavity (from 1.77- to 1.33-fold) and the olfactory region (from 624- to 53.2-fold). The average drug dose deposited in the nasal cavity and the olfactory epithelium region is very similar in the right nasal cavity independent of pulsation conditions (inhalation side). In contrast, the local aerosol dose in the olfactory region of the left side is at least 100-fold lower than that in the nasal cavity independent of pulsation condition. Hence, while pulsatile flow reduces the right-left (inhalation-exhalation) imbalance, it is not able to overcome it. However, the inhalation side (even with pulsation) allows for relatively high olfactory epithelium drug doses per area reaching the same level as in the total nasal cavity. Due to the relatively low drug deposition in olfactory region on the exhalation side, this allows either very efficient targeting of the inhalation side, or uniform drug delivery by performing bidirectional flow first from the one and then from the other side of the nose.

摘要

鼻腔嗅觉区域是药物从鼻上皮直接非侵入性输送到大脑的潜在途径，可绕过通常具有屏障作用的血脑屏障。然而，由于其在鼻腔中的位置，将气雾剂有效输送到嗅觉区域具有挑战性。在此，我们使用基于患者特异性鼻腔几何结构的计算流体动力学（CFD）模型，探索在双向脉动流条件下进行气雾剂输送，以实现向嗅觉区域的靶向药物输送。吸入空气动力学直径为1微米的气雾剂，其大小足以输送足够大的药物剂量，同时又可能小到足以因颗粒扩散和气流振荡等原因实现非惯性气溶胶沉积，通过一个鼻孔吸入1.98秒，然后通过另一个鼻孔呼出。稳定流速为4升/分钟的双向气雾剂输送在鼻腔和嗅觉区域的沉积效率（DE）分别为50.9%和0.48%。平均流速为4升/分钟（频率：45赫兹）的脉动流将这些值分别降至34.4%和0.12%，并减轻了鼻腔（从1.77倍降至1.33倍）和嗅觉区域（从624倍降至53.2倍）左右两侧沉积的不均匀性。在右侧鼻腔中，无论脉动条件如何（吸入侧），沉积在鼻腔和嗅觉上皮区域的平均药物剂量非常相似。相比之下，无论脉动条件如何，左侧嗅觉区域的局部气雾剂剂量比鼻腔中的至少低100倍。因此，虽然脉动流减少了左右（吸入 - 呼出）不平衡，但无法克服这种不平衡。然而，吸入侧（即使有脉动）每单位面积的嗅觉上皮药物剂量相对较高，可达到与整个鼻腔相同的水平。由于呼气侧嗅觉区域的药物沉积相对较低，这使得要么能够非常有效地靶向吸入侧，要么通过先从鼻子的一侧然后从另一侧进行双向流动来实现均匀的药物输送。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/266e/8650014/6149cbd71c03/fphar-12-746420-g013.jpg
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Eur J Pharm Sci. 2018-3-27

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