Challenges of infant pulmonary drug delivery: Aerosol deposition during realistic breathing

Effective inhalation therapy in infants presents significant challenges owing to their distinctive airway anatomy, respiratory patterns, and behavioural factors. This study examined aerosol deposition in a realistic infant airway model under various respiratory conditions, including normal breathing and crying. The airway geometry of a 10-month-old infant was reconstructed from computed tomography scans, and both computational (in silico) and experimental (in vitro) methodologies were employed to analyse aerosol deposition patterns. The findings demonstrated that while a substantial proportion of nebulised aerosol particles (70%) bypassed the upper respiratory tract during stationary inspiration, realistic breathing patterns revealed considerable variations in deposition. Notably, crying significantly increased aerosol deposition in the upper airways. Particle size also exhibited a crucial role, with 5 μm particles demonstrating 50% deposition in the upper airways during normal breathing compared to only 6% for 2.5 μm particles. This observation underscores the suboptimal nature of current inhalation products, which are frequently designed for particle sizes of 1–5 μm. This study provides valuable insights into aerosol delivery in infants, emphasising the need for age-specific inhalation therapy. Modifications in particle size distribution, potentially towards smaller particles (1–2.5 μm), may enhance therapeutic outcomes. Further research is warranted to develop infant-specific airway models and to explore alternative particle designs to optimise inhalation drug delivery in this vulnerable population.