Abstract
Background: Lucinactant for inhalation is an investigational noninvasive, aerosolized surfactant replacement therapy for treatment of preterm neonates with respiratory distress syndrome. Lucinactant for inhalation consists of lyophilized lucinactant and the Aerosurf® Delivery System (ADS). The objective of this study was to characterize the total and regional pulmonary deposition of lucinactant delivered by the ADS in nonhuman primates (NHPs).Methods: Lucinactant was radiolabeled by the addition of technetium-99m (99mTc)-sulfur colloid. The radiolabeled aerosol was characterized and validated using a Mercer cascade impactor. An in vivo deposition study was performed in three cynomolgus macaques. Radiolabeled lucinactant was aerosolized using the ADS and delivered via nasal cannula under 5 cm H2O nasal continuous positive airway pressure (nCPAP) for 5–9 minutes. A two-dimensional planar image was acquired immediately after aerosol administration, followed by a three-dimensional single-photon emission computed tomography (SPECT) image and a second planar image. The images were analyzed to determine the pulmonary (lungs) and extrapulmonary (nose + mouth, trachea, stomach) distribution. The SPECT data were used to determine regional deposition.Results: The radiolabed lucinactant aerosol had a mass median aerodynamic diameter = 2.91 μm, geometric standard deviation (GSD) = 1.81, and an activity median aerodynamic diameter = 2.92 μm, GSD = 2.06. Aerosolized lucinactant was observed to deposit in the lungs (11.4%), nose + mouth (79.9%), trachea (7.3%), and stomach (1.4%). Analysis of the SPECT image demonstrated that the regional deposition within the lung was generally homogeneous. Aerosolized lucinactant was deposited in both the central (52.8% ± 1.2%) and peripheral (47.2% ± 1.2%) regions of the lungs.Conclusion: Aerosolized lucinactant, delivered using the ADS via constant flow nCPAP, is deposited in all regions of the lungs demonstrating that surfactant can be aerosolized and delivered noninvasively to NHPs.
Highlights
Respiratory distress syndrome (RDS) of the newborn is a disease that results from insufficiency of pulmonary surfactant in the immature neonatal lung, which carries a risk of high morbidity and mortality
Several studies have demonstrated that earlier intratracheal surfactant replacement therapy (SRT) is more beneficial than later SRT.[2]. For this reason, guidelines recommend that when SRT is used it be given as early as possible.[3,4,5,6] when nasal continuous positive airway pressure (nCPAP) is used as initial respiratory support, SRT is necessarily delayed in those neonates who require endotracheal intubation
A pilot feasibility study was performed on preterm newborns with moderate RDS requiring singleprong pharyngeal continuous positive airway pressure (CPAP) for the delivery to the infant of nebulized Alveofact at a dose of 150 mg/kg.[49]. The results showed that pharyngeal CPAP alone did not improve ventilation and oxygenation significantly, whereas improvement in oxygenation and alveolar ventilation was noted immediately once nebulization of surfactant was started
Summary
Respiratory distress syndrome (RDS) of the newborn is a disease that results from insufficiency of pulmonary surfactant in the immature neonatal lung, which carries a risk of high morbidity and mortality. Several studies have demonstrated that earlier intratracheal SRT is more beneficial than later SRT.[2] For this reason, guidelines recommend that when SRT is used it be given as early as possible.[3,4,5,6] when nCPAP is used as initial respiratory support, SRT is necessarily delayed in those neonates who require endotracheal intubation. Lucinactant for inhalation is an investigational noninvasive, aerosolized surfactant replacement therapy for treatment of preterm neonates with respiratory distress syndrome. The objective of this study was to characterize the total and regional pulmonary deposition of lucinactant delivered by the ADS in nonhuman primates (NHPs). Conclusion: Aerosolized lucinactant, delivered using the ADS via constant flow nCPAP, is deposited in all regions of the lungs demonstrating that surfactant can be aerosolized and delivered noninvasively to NHPs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
