Pulmonary Surfactant Aerosols for Respiratory Distress

This work will determine the precise manufacturing methods necessary to improve the deliveryof pulmonary surfactant in the treatment of Neonatal Respiratory Distress Syndrome, whilesimultaneously achieving greater cost-effectiveness of the dosage form. Current surfactant preparationsare too viscous for aerosolization and must be delivered to the lung by intratracheal instillation of a large,potentially obstructive bolus which is poorly distributed. By capitalizing on our experience in liposomeproduction and characterization, we will convert an existing surfactant preparation into a submicrondispersion which can be aerosolized into 1-3 micromole droplets. In pilot experiments we have revealeda potential increase in drug efficacy coincident with an almost ten-fold reduction in drug cost. Quantityand distribution of labels incorporated into surfactant lipids in the aerosol will be followed in order todemonstrate more extensive deposition of such aerosols in the lung than that achieved with previoustechniques. Delivery, distribution and efficacy of the aerosolizable surfactant will be demonstrated usinga suit-depleted newborn piglet model. Delivery and distribution will be measured by whole body imagingof radiolabel, while efficacy will be monitored by improvements in blood gas values and in lungcompliance.