Role of lipid polymorphism in pulmonary surfactant.
The development of artificial surfactants for the treatment of respiratory distress syndrome (RDS) requires lipid systems that can spread rapidly from solution to the air-water interface. Because hydration-repulsion forces stabilize liposomal bilayers and oppose spreading, liposome systems that undergo geometric rearrangement from the bilayer (lamellar) phase to the hexagonal II (HII) phase could hasten lipid transfer to the air-water interface through unstable transition intermediates. A liposome system containing dipalmitoylphosphatidylcholine was designed; the system is stable at 23 degrees C but undergoes transformation to the HII phase as the temperature increases to 37 degrees C. The spreading of lipid from this system to the air-water interface was rapid 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 functioning of pulmonary surfactant.
Perkins
W R
WR
The Liposome Company, Inc., 1 Research Way, Princeton, NJ 08540, USA.
Dause
R B
RB
Parente
R A
RA
Minchey
S R
SR
Neuman
K C
KC
Gruner
S M
SM
Taraschi
T F
TF
Janoff
A S
AS
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002784:Cholesterol / Q000737:chemistry* / Q000494:pharmacology; D008051:Lipid Bilayers; D008081:Liposomes / Q000737:chemistry* / Q000494:pharmacology; D008170:Lung Compliance / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D010714:Phosphatidylethanolamines / Q000737:chemistry* / Q000494:pharmacology; D011663:Pulmonary Surfactants / Q000737:chemistry* / Q000494:pharmacology; D011817:Rabbits; D013499:Surface Properties; D013500:Surface Tension; D013696:Temperature; D014961:X-Ray Diffraction
D008051:Lipid Bilayers; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C020888:1,2-dielaidoylphosphatidylethanolamine; D002784:Cholesterol