(286a) Dynamic Surface Tension and Dispersion Stability of Aqueous Lipid/Protein Dispersions

A mixture of lipid and protein compounds called ?lung surfactant? concentrates, or adsorbs, at the interface of an aqueous layer which lines the lung alveoli. Dipalmitoylphosphatidylcholine (DPPC) lipid is zwitterionic, insoluble, and the major component of natural lung surfactant and of some commercial synthetic lung surfactant replacement formulations. Sonicated dispersions of DPPC vesicles at 0.1 wt% (1000 ppm) in aqueous isotonic buffer solutions produced previously (S. H. Kim, Y. Park, S. Matalon, and E.I. Franses, 2008, Colloids and Surfaces B, 67: 253-260) are colloidally stable for hours and days, and they have very low (< 10 mN/m) dynamic surface tension minima (DSTM) under pulsating area condition at 37 and 25º C. The vesicles are stabilized in part electrostatically due to negative charge from adsorbed ions (zeta potential = -20±3 mV), and in part by other forces.

The DPPC dispersions may also have to be colloidally stable and produce low DSTM in the presence of blood serum proteins such as albumin or fibrinogen, because such proteins can be released from the blood stream to the alveolar lining layer when the lung alveolar tissue is injured. When a stable solution of 1000 ppm BSA (bovine serum albumin), which is negatively charged, is mixed with a DPPC vesicle dispersion, it becomes colloidally unstable, aggregating within minutes and hours. This implies some heterocoagulation. The DSTM's become much higher because the protein may adsorb more than the lipid at the surface and may block in part the adsorption of the lipid and the lowering of the DST.

DPPC lipid vesicles have been modified to reduce the possibility of aggregation with the protein by the addition of a small weight fraction of a neutral lipid with PEG (polyethyleneglycol) groups. The mixed lipid vesicles were found to be more stable than DPPC, remaining stable for months. Moreover, the mixed vesicles show no tendency to aggregate with the albumin molecules for days, probably because of a steric repulsive mechanism. The mixed vesicles are, therefore, more ?biocompatible.? Finally, the mixed lipid dispersions have low DSTM without or with the albumin.