Structure and stability of liposomes : Interactions with micelle- forming surfactants

Sammanfattning: The stability of phospholipid lipomes interacting with micelle-forming surfactants was studied under physiological conditions (150 mM NaCl and pH=7.4 unless otherwise stated) mainly by use of cryo-TEM and fluorescence. The pH-dependent phase propensity of oleic acid was shown to determine the phase behaviour when added to preformed egg-lecithin (EPC) liposomes. Micelles were formed at high pH when the fatty acid was deprotonated, while dispersed inverted structures were formed at lower pH.Alkyl sulphates with a hydrocarbon chain length of 12 or 14 carbons induced formation of defect (or holey) lamellar liposomes as intermediate structures when added to sonicated liposomes of egg-lecithin in 150 mM NaCl. The shorter C10SO4- surfactant instead formed cylindrical micelles as intermediates. At ionic strengths of 100 mM NaCl or less, C14SO4- induced small discoid micelles.The micelle-forming PEG(2000)-PE lipid, commonly used for the purpose of steric stabilisation, induced transitions of liposomes into bilayer fragments at concentrations of 8-10 mol% for the lipids investigated. Inclusion of cholesterol did not affect this general behaviour. At concentrations of 5 mol% and 8 mol% PEG-PE the intact cholesterol containing liposomes were less permeable to the hydrophilic dye carboxyfluorescein, while the presence of PEG lipids did not affect the leakage of the more hydrophobic ethidium.A number of PEO-PPO-PEO triblock copolymers were found to have severe drawbacks for the purpose of drug delivery. Pure EPC liposomes were structurally destabilised at low polymer to lipid molar rations (≈ 0.02). When cholesterol was included there were no visible structural defects, but the polymers still induced an increase in permeability of carboxyfluorescein. In addition, there were no indications of effective steric stabilisation.