Small, but not large, unilamellar liposomes composed of dioleoylphosphatidylethanolamine and oleic acid can be stabilized by human plasma

Abstract

Small unilamellar liposomes, composed of dioleoylphosphatidylethanolamine (DOPE) and oleic acid (OA), prepared by sonication, were incubated in the presence of human plasma at 37 degrees C. The release of entrapped calcein after 8-h incubation was about 15% in plasma, compared with about 70% in phosphate-buffered saline under the same conditions. In contrast, dioleoylphosphatidylcholine (DOPC)/OA liposomes under the same conditions release about 70% in plasma and only 10% in PBS. Total release of calcein from the DOPE/OA liposomes was observed in a PBS solution containing bovine serum albumin, and the release was completely blocked by preincubation of the liposomes with plasma. These results indicate that the unstable DOPE/OA liposomes are stabilized by incubation with plasma. The stabilization process was very fast, being completed within 1 min. Only relatively small liposomes (d less than or equal to 200 nm) were completely stabilized by plasma; larger liposomes were progressively less stabilizable. SDS-polyacrylamide gel electrophoresis of liposomes which had been incubated with plasma and then washed indicated that several proteins were tightly associated with liposomes. Using liposomes containing [14C]OA, it was found that about 70% of the original OA was extracted after 1-h incubation with human plasma at 37 degrees C. Thin-layer chromatographic analysis of the plasma-treated liposomes showed the presence of the plasma lipids in the liposomes. These results suggest that liposomes composed of DOPE/OA are stabilized by protein and/or lipid components from human plasma and that the composition of the liposomes is altered. The mechanism of stabilization is discussed in terms of the surface pressure of small vesicles with a high degree of curvature.(ABSTRACT TRUNCATED AT 250 WORDS)