Rapid and Efficient Aerosol Delivery During 60 L/min High Flow Nasal Cannula Therapy—In Vitro Development of a Novel Dry Powder Delivery Platform

Abstract

High flow therapy (HFT) delivers heated and humidified gas at flow rates up to 60 L/min to hypoxemic subjects, but is not conducive to simultaneous administration of pharmaceutical aerosols. Aerosol losses occur due to circuit wall impaction, environmental loss and particle growth from high humidity; resulting in poor lung delivery efficiency. This study compares two strategies for delivering dry powder aerosols during 60 L/min humidified HFT: a circuit connector (HFT-CC) which integrates directly into the standard HFT flow pathway, and an interface connector (HFT-IC) designed to bypass delivery line losses by directly injecting aerosol into the nasal prongs. Experiments were conducted using an anatomically-realistic in vitro adult nasal airway model with physiological breathing patterns, albuterol sulfate excipient enhanced growth (AS-EEG) dry powder formulation, air-jet aerosolization engine, and custom air actuation system. The HFT-CC approach improved lung delivery to 25.6% compared to existing published data (12.8%) but was limited by losses in the circuit tubing and nasal interface. The HFT-IC approach with a split nasal interface achieved 45.1% lung delivery (HFT-IC3), nearly a fourfold improvement from previously published results, by isolating aerosol flow from HFT flow and eliminating upstream losses. While nose-throat (NT) deposition in HFT-IC3 remained high (39.6%), this approach presents an attractive target for future computational and experimental optimization. These findings prove that efficient dry powder aerosol lung delivery during 60 L/min humidified HFT is achievable, laying the groundwork for translational advances in the efficient delivery of pulmonary therapies such as surfactants, antibiotics, anti-inflammatories, and antivirals during ventilatory support.

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