In silico optimization of targeted aerosol delivery in upper airways via Inhaled Volume Tracking

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.