Background

Despite the widespread use of aerosol inhalation as a drug delivery method, targeted delivery to the upper airways remains an ongoing challenge in the quest for improved clinical response in respiratory disease.

Methods

Here, we examine in silico flow and particle dynamics when using an oral Inhaled Volume Tracking manoeuvre. A short pulsed aerosol bolus is injected during slow inhalation flow rates followed by clean air, and a breath-hold is initiated once it reaches the desired depth. We explore the fate of a broad particle size range (1–40 μm) for both upright and supine positions.

Findings

Our findings illustrate that despite attempts to mitigate dispersion using slower flow rates, the laryngeal jet disperses the aerosol bolus and thus remains a hurdle for efficient targeted delivery. Nevertheless, we show a decrease in extra-thoracic deposition; large aerosols in the range of 10–30 μm potentially outperform existing inhalation methods, showing deposition fractions of up to 80% in an upright orientation.

Interpretation

The improved deposition during Inhaled Volume Tracking shows promise for clinical applications and could be leveraged to deliver larger payloads to the upper airways.

中文翻译：

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通过吸入量跟踪对上呼吸道中的目标气溶胶输送进行计算机优化。

背景

尽管气溶胶吸入作为一种药物递送方法被广泛使用，但在寻求改善呼吸系统疾病临床反应的过程中，靶向递送至上呼吸道仍然是一个持续的挑战。

方法

在这里，我们在使用口服吸入体积跟踪操作时检查了电子流和粒子动力学。在缓慢吸入流速期间注入短脉冲气溶胶丸剂，然后注入清洁空气，一旦达到所需深度，就开始屏气。我们探索了直立和仰卧位的宽粒径范围 (1-40 μm) 的命运。

发现

我们的研究结果表明，尽管尝试使用较慢的流速来减轻扩散，但喉部射流会分散气溶胶丸剂，因此仍然是有效靶向递送的障碍。尽管如此，我们发现胸外沉积物有所减少；10-30 μm 范围内的大型气溶胶可能优于现有的吸入方法，在直立方向上的沉积比例高达 80%。

解释

吸入量跟踪过程中改善的沉积显示出临床应用的前景，并可用于向上呼吸道输送更大的有效载荷。