Charge boosting effect of cholesterol on cationic liposomes

Cationic liposomes that have been used as drug or gene delivery vehicles can be obtained by mixing cationic surfactants in phospholipid liposomes. Cytotoxicity of cationic molecules is one of the problems of the cationic nanocarriers. Therefore we aimed to formulate highly positively-charged cationic liposomes with low content of cationic surfactant, which have both higher cellular uptake ability and lower cytotoxicity. We have investigated the zeta potential behavior in water/soy bean lecithin/cationic surfactant/cholesterol systems by the changing composition as well as the molecular structure of the cationic surfactant. Mixing of monoalkyl (C-12, C-16 and C-18) and dialkyl (C-12 and C-18) quaternary ammonium chlorides were increased the zeta potential of liposomes from negative to positive values (more than +50 mV). Mixing the cholesterol into the cationic liposomes increased the maximum zeta potential further and also induced the large shift of the negative-positive transition point with respect to the cationic surfactant mixing fraction. It means much less cationic surfactant is needed to obtain highly positively-charged liposomes. The significant cholesterol effects on the zeta potential of liposomes were explained based on the lipid distribution inhomogeneity caused by the increased fluidity of liquid ordered phase membranes and the large critical packing parameter of the negatively-charged lipid. (C) 2016 Elsevier B.V. All rights reserved.