Development of a New Dry Powder Aerosol Synthetic Lung Surfactant Product for Neonatal Respiratory Distress Syndrome (RDS) - Part II: In vivo Efficacy Testing in a Rabbit Surfactant Washout Model.

Abstract

PURPOSE: Surfactant therapy incorporates liquid bolus instillation via endotracheal tube catheter and a mechanical ventilator in preterm neonates with respiratory distress syndrome (RDS). Aerosolized surfactants have generated interest and conflicting data on the efficacy of phospholipid (PL) dose requirements. We developed and characterized a synthetic lung surfactant excipient enhanced growth (SLS-EEG) dry powder aerosol product. In this study, we compare the in vivo performance of the new aerosol product with standard-of-care liquid instillation. METHODS: Juvenile rabbits were sedated, anesthetized, intubated, and ventilated. Endogenous surfactant was depleted via whole lung lavage. Animals received either a standard dose of liquid Curosurf (200&#xa0;mg PL/kg) instilled via a tracheal catheter, SLS-EEG powder aerosol (60&#xa0;mg device loaded dose; equivalent to 24&#xa0;mg PL/kg), or sham control. Gas exchange, lung compliance, and indices of disease severity were recorded every 30&#xa0;min for 3.5&#xa0;h and macro- and microscopy images were acquired at necropsy. RESULTS: While aerosol was administered at an approximately tenfold lower PL dose, both liquid-instilled and aerosol groups had similar, nearly complete recoveries of arterial oxygenation (PaO; 96-100% recovery) and oxygenation index, and the aerosol group had superior recovery of compliance (P&#x2009;<&#x2009;0.05). The SLS-EEG aerosol group showed less lung tissue injury, greater uniformity in lung aeration, and more homogenous surfactant distribution at the alveolar surfaces compared with liquid Curosurf. CONCLUSIONS: The new dry powder aerosol SLS product (which includes the delivery strategy, formulation, and delivery system) has the potential to be a safe, effective, and economical alternative to the current clinical standard of liquid bolus surfactant instillation.