(462b) Interactions of Dilauroylphosphatidylcholine (Dlpc) Lipid Vesicles with Albumin in Aqueous Solutions

Vesicles of zwitterionic (one cationic group, one anionic group, no net molecular charge) DLPC, in water or in phosphate-buffered saline (?buffer?), at 25 degrees C are fluid (chain melting temperature, T = 0 degrees C), and kinetically fairly stable, with their average sizes increase slowly with time. In water or buffer, the average size is 150 nm and 200 nm, respectively, as determined with dynamic light scattering (DLS) and spectroturbidimetry. The vesicles have a positive charge in water (pH= 8), and are nearly neutral at physiological pH of 7. Albumin is negatively charged (isoelectric point of 4.9) in water (pH = 5.5) and in buffer (pH = 7). When DLPC vesicles are mixed with aqueous albumin, the dispersion turbidity and the particle diffusivity from dynamic light scattering, increase, indicating substantial heterocoagulation. The initial sizes are ~250 nm. The resulting lipid-protein aggregates are negatively charged, as inferred from electrophoresis, and continue coagulating slowly in buffer. The results have implications in designing lipid formulations to treat the adult or acute respiratory distress syndrome (ARDS). In this syndrome, some serum proteins leak in the alveolar lining layer and may inhibit the surface-tension-lowering ability of the lipid formulations [Phang, T.-L. and Franses, E. I., J. Colloid Interface Sci., 275, 477 (2004); Phang, T.-L., McClellan, S. J., and Franses, E. I., Langmuir, 21, 10140 (2005)]. The results also have important implications in using vesicular dispersions for delivery of soluble proteins or peptides drugs to the lungs or the bloodstream.