QUALITY-CONTROL OF LIPOSOMAL LIPIDS WITH SPECIAL EMPHASIS ON PEROXIDATION OF PHOSPHOLIPIDS AND CHOLESTEROL

The usefulness of various assays for the determination of phospholipid and cholesterol peroxidation in liposome formulations was studied on model liposomes prepared as small unilamellar vesicles (SUV) and multi lamellar vesicles (MLV) from either native egg phosphatidylcholine (EP C), partially hydrogenated egg phosphatidylcholine (PHEPC) or fully hy drogenated egg phosphatidylcholine (HEPC) and cholesterol in 65/35 mol ar ratio at a total lipid concentration of 10 mumol/ml in phosphate bu ffered saline pH 7.2. Liposomes were incubated at 50-degrees-C for a t otal of 3 months. Fatty acid and cholesterol peroxidation were monitor ed after 1, 2 and 3 months by quantitative measurement of fatty acids and cholesterol and as well as peroxidation products. Fatty acid perox idation products malondialdeyde, lipidhydroperoxides, conjugated diene s, conjugated trienes were poor predictors of actual fatty acid loss. Among the cholesterol peroxidation products 7-hydroxy-cholesterols, 7- keto-cholesterol and 4-cholesten-3-one were measured quantitatively. O nly the formation of 7-keto-cholesterol correlated well with cholester ol disappearance.