Development of a New Aerosol Delivery System for Administering Aerosol Surfactant Therapy to Preterm Infants Through...

In this study, aerosol surfactant therapy administered through a laryngeal mask airway (LMA) was investigated as an alternative to the more invasive approach of surfactant liquid bolus instillation, which carries significant risks to infants with respiratory distress syndrome. Combining a recently developed synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder formulation with a novel LMA aerosol delivery system (LMA-ADS) was intended to avoid the side effects associated with current liquid bolus therapies. A new patient connection system (PCS) was developed for introducing the aerosol from an infant air-jet DPI into the LMA. Using in vitro benchtop studies with a 1.5 kg preterm infant extrathoracic model, the effectiveness of a co-flow (CF) strategy was investigated for improving lung delivery efficiencies of the aerosol. Next, different tubing sizes and aerosolization parameters were explored using laser diffraction to quantify their effects on aerosol size distribution metrics, and insights gained were implemented to develop four PCS designs. The best-performing PCS was tested with a realistic pulmonary mechanics (PM) model. Large-diameter tubing (> 1 mm diameter) was shown to produce large aerosol size increases that could be minimized with smaller-diameter tubing. Following integration of 0.8 mm inner diameter tubing, all PCS designs were capable of at least ~ 24% lung delivery efficiency (based on loaded dose) with the best-performing PCS reaching ~ 29%, which represented a > 1.7-fold improvement from baseline. PM simulations confirmed safe delivery pressures with only minor reductions in aerosol transmission. Therefore, the LMA-ADS could be a promising alternative for effective aerosol surfactant therapies.