(162u) Effect of Preparation Method on the Formation of Multilamellar Liposomes and Unilamellar Vesicles of Dilauroylphosphatidylcholine

When dispersions of fluid liposomes of dilauroylphosphatidylcholine (DLPC) lipid, in water or in phosphate-buffered saline solution, are stirred vigorously, the liposomes become smaller, with average sizes around 0.5 to 3 microns, as evidenced by dynamic light scattering (DLS) and spectroturbidimetry. Small-angle X-ray scattering (SAXS) data and modeling reveal mostly multilamellar liposomes (?onions? or ?liposomes?) with repeat interlamellar distance D = 5.8 nm. SAXS for these dispersions also shows evidence of unilamellar vesicles (?vesicles?), which are confirmed by cryogenic transmission electron microscopy (cryo-TEM) and freeze-fracture-replication TEM, to have sizes ranging from 0.5 to 6 microns . When these dispersions are sonicated extensively to a low and constant turbidity, transparent to the eye, the resulting aggregates are not only vesicles, as is normally assumed. SAXS and cryo-TEM reveal clear evidence of some small, 200-400 nm, liposomes, in addition to the expected vesicles of a wide size distribution, from 15 to 200 nm. The bilayer thickness, from SAXS, is 4.6 nm. These results are important for lung surfactant replacement applications, because the liposome or vesicle sizes affect the dynamic surface tension [Pinazo, A., Wen, X., Liao, Y.-C., Prosser, A. J., and Franses, E. I., Langmuir, 18, 8888 (2002); Phang, T.-L., Liao, Y.-C., and Franses, E. I., Langmuir, 20, 4004 (2004)]. They also are relevant in designing liposome-based or vesicle-based drug delivery vehicles for respiratory or cancer therapies.