Physicochemical and immunological properties of albumin-associated dialkyl-ether phosphatidylcholine liposomes

Multilamellar and unilamellar liposomes were prepared from sn-3-dihexadecylphosphatidylcholine/cholesterol/dicetylphosphate (7:2:1) in the presence of bovine serum albumin. Liposome-associated bovine serum albumin was separated from free bovine serum albumin by Blue Sepharose CL-6B affinity column chromatography. The chromatographed fractions were analyzed for their protein and liposomal phosphorus contents. The recovered albumin-containing liposomes were characterized morphologically by electron microscopy on negatively stained preparations. These preparations showed vesicular organizations of multilamellar or unilamellar phospholipid bilayers depending on the method of preparation used in each case. An analysis of the particle size distribution indicated that the mean radius was 280 +/- 50 nm for the multilamellar bovine serum albumin-liposomes and 150 +/- 50 nm for the unilamellar preparations. The efficacy of unilamellar and multilamellar dialkyl-ether phosphatidylcholine liposomes in eliciting antibody formation was examined. Mice were injected with liposome-entrapped bovine serum albumin and the albumin-specific plaque-forming cell response was evaluated. The unilamellar vesicles were found to be more effective than their multilamellar counterparts in promoting the elicitation of the anti-bovine serum albumin plaque-forming cell response. Within each category of lamellar structure, i.e., unilamellar or multilamellar bilayers, liposomes composed of dialkyl-ether phosphatidylcholines are less efficient than those of diacyl-ester phosphatidylcholines in potentiating the humoral immune response. These results demonstrate that liposome-mediated enhancement of the antibody response is determined, at least in part, by the lamellar arrangement of the vesicles and by the characteristic chemical structures of the phospholipids used.