title: Damage to liposomal lipids: protection by antioxidants and cholesterol-mediated dehydration.
abstract: Liposomes composed of egg phosphatidylcholine (EPC) (13.4%, of the acyl chains being polyunsaturated fatty acids (PUFA)) and EPC/cholesterol (10:1 mol/mol) were studied for factors that affect liposomal lipid oxidative damage and hydrolysis upon long-term (16 months) storage. Factors studied include: (1) levels of lipid/water interface hydration, related to the presence of cholesterol in the lipid bilayer; (2) the membrane-associated antioxidant vitamin E; (3) the water-soluble antioxidant Tempol; and (4) exposure to light. Liposomal dispersions were stored at room temperature, either exposed to or protected from daylight, for a period of 16 months. Chemical and physical changes were monitored at several time points to assess oxidative and hydrolytic degradation of liposomal lipids. The conclusions of the study are: (1) PUFA are the most sensitive component of the liposome bilayer to oxidative degradation damage during long-term storage; (2) EPC liposomes are more sensitive to degradation during storage than EPC cholesterol liposomes, the presence of cholesterol in the lipid bilayer having a protective effect, probably due to its effect in decreasing the lipid-bilayer hydration; (3) oxidative degradation is the major process during long-term storage, having an earlier onset than the hydrolytic degradation: and (4) Tempol provided significantly better protection than vitamin E to EPC liposomal PUFA against oxidative damage during long-term storage. The relevance of cholesterol's presence, as a 'drying agent', in membranes containing PUFA to resistance of biological membranes to oxidative damage is discussed.
authors.affiliation: Department of Biochemistry, Hebrew University-Hadassah Medical School, Jerusalem, Israel. samunia@cc.huji.ac.il
authors.forename: A M
authors.initials: AM
authors.lastname: Samuni
authors.forename: A
authors.initials: A
authors.lastname: Lipman
authors.forename: Y
authors.initials: Y
authors.lastname: Barenholz
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism*; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D003497:Cyclic N-Oxides / Q000032:analysis / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005456:Fluorescent Dyes / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007848:Laurates / Q000494:pharmacology; D008027:Light; D008051:Lipid Bilayers / Q000737:chemistry; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008081:Liposomes / Q000378:metabolism*; D008563:Membrane Lipids / Q000737:chemistry; D010063:Ovum / Q000737:chemistry; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000032:analysis / Q000494:pharmacology; D013113:Spin Labels; D013997:Time Factors; D014810:Vitamin E / Q000032:analysis / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D005231:Fatty Acids, Unsaturated; D005456:Fluorescent Dyes; D007848:Laurates; D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D011837:Radiation-Protective Agents; D013113:Spin Labels; D014810:Vitamin E; D002784:Cholesterol; D015081:2-Naphthylamine; C001803:tempol; C065580:laurdan