Effect of a PEGylated Lipid on the Dispersion Stability and Dynamic Surface Tension of Aqueous DPPC and on the Interactions with Albumin

Abstract

Dispersions of dipalmitoylphosphatidylcholine (DPPC) vesicles at 0.1 wt % (1000 ppm) in aqueous isotonic buffer solutions produced by extensive sonication were found to be colloidally stable for hours and days. They also had very low (<10 mN/m) dynamic surface tension minima (DSTM) under pulsating area conditions at 37 degrees C at 20 rpm area pulsation rate. When a 1000 ppm DPPC dispersion was mixed with a stable solution of 1000 ppm bovine serum albumin (BSA), it became colloidally unstable, aggregating within minutes, implying that heterocoagulation between lipid vesicles and albumin takes place. The heterocoagulated dispersion produced high DSTM because the lipid transport rate to the interface became slower. Moreover, the protein may have been transported to the surface faster and adsorbed more than the lipid at the surface. DPPC lipid vesicles were modified for reducing aggregation with other vesicles or with the protein with the addition of a small weight fraction of a neutral "PEGylated" lipid, with a covalently bonded poly(ethylene glycol) (PEG) group. The mixed vesicles were found to be quite more stable than the DPPC vesicles, remaining stable for months, apparently stabilized by steric forces. The colloidal stability at the initial stages of coagulation was evaluated quantitatively from the Fuchs-Smoluchowski stability ratio W. When the modified lipid vesicle dispersion was mixed with the albumin, the vesicles showed no tendency to aggregate with the albumin molecules for days, also probably because of steric repulsion between the PEGylated lipid and the protein. Finally, the mixed lipid dispersions maintained their low DSTM as did the DPPC vesicles without the albumin, and also in the presence of albumin. The results have implications on the use of DPPC or DPPC-based lipids in treating alveolar respiratory diseases without albumin inhibition of their surface tension lowering ability.