(408a) Dispersion Stability and Dynamic Surface Tension of Aqueous DPPC and Interactions with Albumin

When dispersions of dipalmitoylphosphatidylcholine (DPPC) vesicles in aqueous isotonic buffer solutions are produced by extensive sonication, they are quite stable colloidally, for hours and days. They also have low (<10 mN/m) dynamic surface tension minima (DSTM) under pulsating area conditions at 37 °C [1]. When a 1000 ppm DPPC dispersion is mixed with a stable solution of 1000 ppm bovine serum albumin (BSA), aggregates appear within minutes. This implies that heterocoagulation between lipid vesicles and albumin molecules takes place. Then DSTM becomes higher, because the aggregates are larger and diffuse more slowly to the interface. Moreover, the dissolved protein may transport to the air/water surface faster, and adsorb more, than the lipid at the surface. In order to reduce the vesicle-vesicle and vesicle-albumin aggregation rates, the vesicles were modified with the addition of a small weight fraction of a neutral PEGylated lipid, containing an attached polyehyleneglycol chain [2]. The mixed ? hairy? lipid vesicles were much more stable than the DPPC vesicles, remaining stable for months, and they were apparently stabilized sterically. The colloidal stability at the initial stages of coagulation was evaluated quantitatively from the Fuchs-Smoluchowski stability ratio W as obtained from DLS (dynamic light scattering) data [2,3]. The mixed lipid vesicles show no tendency to aggregate with the albumin molecules for days, when their particle sizes and shapes were monitored with spectroturbidimetry and electron microscopy, probably because of steric repulsions. Furthermore, the mixed lipid dispersions maintain their low DSTMs with albumin. Various weight ratios of albumin to lipid, from 1 to 1000, were tested to gauge the aggregate stoichiometry. The results suggest that albumin molecules act as ?glue? to bind large numbers of vesicles, which precipitate. The mixed hairy vesicles coagulate much more slowly when in contact with albumin. The results have implication in producing effective formulations for treating ARDS (Acute Respiratory Distress Syndrome). Such formulations should be stable for long times and maintain their ability to produce low DSTMs.

1. Kim, S. H., Park, Y., Matalon, S., Franses, E. I. (2008) Colloids and Surfaces B, 67, 253-260. 2. Park, Y. and Franses, E. I. (2010) Langmuir, Article in Press. 3. Park, Y., Huang, R., Corti, D. S., Franses, E. I. (2010) Journal of Colloid and Interface Science, 342, 300-3010.