The pulmonary route presents an attractive delivery pathway for topical treatment of lung diseases. While significant progress has been achieved in understanding the physical underpinnings of aerosol deposition in the lungs, our ability to target or confine the deposition of inhalation aerosols to specific lung regions remains meagre. Here, we present a novel inhalation proof-of-concept in silico for regional targeting in the upper airways, quantitatively supported by computational fluid dynamics (CFD) simulations of inhaled micron-sized particles (i.e. 1-10 μm) using an intubated, anatomically-realistic, multi-generation airway tree model. Our targeting strategy relies on selecting the particle release time, whereby a short-pulsed bolus of aerosols is injected into the airways and the inhaled volume of clean air behind the bolus is tracked to reach a desired inhalation depth (i.e. airway generations). A breath hold maneuver then follows to facilitate deposition, via sedimentation, before exhalation resumes and remaining airborne particles are expelled. Our numerical findings showcase how particles in the range 5-10 μm combined with such inhalation methodology are best suited to deposit in the upper airways, with deposition fractions between 0.68 and unity. In contrast, smaller (< 2 μm) particles are less than optimal due to their slow sedimentation rates. We illustrate further how modulating the volume inhaled behind the pulsed bolus, prior to breath hold, may be leveraged to vary the targeted airway sites. We discuss the feasibility of the proposed inhalation framework and how it may help pave the way for specialized topical lung treatments.

中文翻译：

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使用脉冲气溶胶丸剂和吸入量跟踪方法将药物靶向输送到上呼吸道

肺部途径为肺部疾病的局部治疗提供了一种有吸引力的递送途径。虽然在了解肺部气溶胶沉积的物理基础方面取得了重大进展，但我们将吸入气溶胶沉积或限制在特定肺部区域的能力仍然很弱。在这里，我们提出了一种新的计算机吸入概念验证，用于上呼吸道的区域定位，通过使用插管的解剖学上的插管吸入微米级颗粒（即 1-10 微米）的计算流体动力学 (CFD) 模拟定量支持- 逼真的多代气道树模型。我们的目标策略依赖于选择粒子释放时间，借此将短脉冲气溶胶丸剂注入气道，并跟踪丸剂后吸入的清洁空气量以达到所需的吸入深度（即气道生成）。然后进行屏气操作以通过沉降促进沉积，然后呼气恢复并排出剩余的空气传播颗粒。我们的数值研究结果展示了 5-10 μm 范围内的颗粒与这种吸入方法相结合如何最适合沉积在上呼吸道，沉积分数在 0.68 和 1 之间。相比之下，较小 (< 2 μm) 的颗粒由于其缓慢的沉降速率而不是最佳的。我们进一步说明了如何在屏气之前调节脉冲推注后吸入的体积，以改变目标气道部位。