ROLE OF LIPID POLYMORPHISM IN PULMONARY SURFACTANT

The development of artificial surfactants for the treatment of respira tory distress syndrome (RDS) requires lipid systems that can spread ra pidly from solution to the air-water interface, Because hydration-repu lsion forces stabilize liposomal bilayers and oppose spreading, liposo me systems that undergo geometric rearrangement from the bilayer (lame llar) phase to the hexagonal II (H-II) phase could hasten lipid transf er to the air-water interface through unstable transition intermediate s. A liposome system containing dipalmitoylphosphatidylcholine was des igned; the system is stable at 23 degrees C but undergoes transformati on to the H-II phase as the temperature increases to 37 degrees C. The spreading of lipid from this system to the air-water interface was ra pid at 37 degrees C but slow at 23 degrees C, When tested in vivo in a neonatal rabbit model, such systems elicited an onset of action equal to that of native human surfactant. These findings suggest that lipid polymorphic phase behavior may have a crucial role in the effective f unctioning of pulmonary surfactant.