N-palmitoylphosphatidylethanolamine stabilizes liposomes in the presence of human serum: effect of lipidic composition and system characterization.
Liposomes containing negatively-charged phospholipid, N-palmitoylphosphatidylethanolamine (NPPE) were examined for stability in the presence of human serum, using the release of the entrapped 5,6-carboxyfluorescein as an aqueous marker. Either small unilamellar vesicles (SUV) or large unilamellar vesicles (LUV) were used. Incorporation of NPPE into PC SUV decreases leakage in the presence of serum or phosphate-buffered saline, no strictly related to size increase observed and to the surface negative charge present. The stabilizing effect of NPPE and Chol were synergistic. Inhibition of destabilization induced by serum of PC/Chol liposomes was observed when NPPE concentrations were above 12 mol%. Change in the membrane fluidity or incorporation of a monosialoganglioside into liposomes do not significantly change the half-life of liposomes in the presence of a high NPPE concentration. Incorporation of NPPE into PC/Chol liposomes increases membrane rigidity which does not change after serum incubation. The presence of NPPE in liposomes decreases lipid transfer/exchange between liposomes and lipoproteins although the same amount of serum proteins were incorporated as in PC/Chol liposomes. As expected, these proteins are accessible to trypsin digestion. In accordance with these results, the liposome agglutination assay shows no steric barrier activity. As a whole, the results obtained in this paper suggest a complex mechanism for stabilization of NPPE containing liposomes in human serum.
Mercadal
M
M
Departamento de Bioquímica y Fisiología, Facultad de Química, Universidad de Barcelona, Spain.
Domingo
J C
JC
Bermudez
M
M
Mora
M
M
De Madariaga
M A
MA
D001769:Blood; D001798:Blood Proteins / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism / Q000494:pharmacology; D004355:Drug Stability; D004357:Drug Synergism; D004563:Electrochemistry; D005677:G(M1) Ganglioside / Q000494:pharmacology; D005732:Gangliosides / Q000737:chemistry; D006207:Half-Life; D006801:Humans; D008055:Lipids / Q000032:analysis*; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008246:Lysophospholipids / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D008560:Membrane Fluidity; D010713:Phosphatidylcholines / Q000378:metabolism; D010718:Phosphatidylserines / Q000494:pharmacology; D017785:Photons; D013057:Spectrum Analysis; D014357:Trypsin / Q000378:metabolism
D001798:Blood Proteins; D005732:Gangliosides; D008055:Lipids; D008081:Liposomes; D008246:Lysophospholipids; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; C025447:sialogangliosides; C067565:1-palmitoylphosphatidylethanolamine; D005677:G(M1) Ganglioside; D002784:Cholesterol; D014357:Trypsin