The I-neb Adaptive Aerosol Delivery System Enhances Delivery of α1-Antitrypsin with Controlled Inhalation

Background: Inhaled alpha 1-antitrypsin (AAT) is being developed for treatment of cystic fibrosis to protect the lungs from excessive free elastase. High drug costs mandate a very efficient aerosol system to deliver a high payload to the airways. The I-neb Adaptive Aerosol Delivery (AAD) System is a portable, electronic, vibrating mesh nebulizer that delivers aerosol only during inhalation. It can be operated in conventional tidal breathing mode (TBM) or in target inhalation mode (TIM) that guides the patient to inhale deeply and slowly. The purposes of this in vitro study were to determine aerosol characteristics, device efficiency, and delivery time of AAT using the I-neb AAD System with TBM and TIM. Methods: We studied the I-neb AAD System in TBM and TIM (inspiratory time 6 or 9 sec) using a breath simulator. The loaded dose was 0.5mL AAT (50mg/mL). Nebulized drug captured on an inspiratory filter was reported as emitted dose. Particle size was measured by laser diffraction. Predicted lung doses were calculated based on the results of a prior scintigraphy study of the I-neb AAD System. Results: Particle size (VMD) for TBM and TIM was similar (4.4-4.8 mu m). The emitted doses were very high and similar between modes (82-90% of loaded dose). Predicted lung dose of AAT ( percent of loaded dose) and delivery times were: TBM 56.6% in 7.5 min; TIM-6 59.9% in 4.4 min; and TIM-9 64.5% in 2.5 min. Conclusions: The I-neb AAD System enhanced AAT delivery by inhalation-only aerosol generation and a low-residual dose. Predicted lung dose was high for both TBM and TIM, but longer inspiratory times with TIM reduced the administration time to one-third that of tidal breathing. We conclude that slow, deep, controlled inspirations using the I-neb AAD System is an efficient method to deliver AAT.