title: The effect of tocopherol on the structure and permeability of phosphatidylcholine liposomes.
abstract: There are numerous phospholipid formulations that incorporate α-tocopherol as a stabilizing agent but there are few studies of the effect of α-tocopherol on phospholipid structure and bilayer permeability. This study uses synchrotron X-ray powder diffraction methods to investigate how α-tocopherol changes the structure of distearoylphosphatidylcholines bilayers. Increasing proportions of α-tocopherol up to 20 mol% induces ripple structures in the bilayers. Two types of ripple structure are produced which are seen in electron micrographs of freeze-fracture replicas with periodicities of 16 and 12 nm, respectively. The stoichiometry of phospholipid: α-tocopherol in the ripple structures at 37 °C is 8:1. The presence of α-tocopherol tends to reduce the angle of tilt of the hydrocarbon chains of the phospholipid in the gel phase from about 34° to the bilayer normal at 20 °C into a more vertical orientation. Increasing proportions of α-tocopherol progressively decrease the temperature of the gel to liquid-crystal phase transition of the phospholipid. The presence of up to 20 mol% α-tocopherol in 1-palmitoyl-2-oleoyl-phosphocholine inhibits leakage of phenol red dye from liposomes. The effect of 7 mol% α-tocopherol on leakage was compared with phospholipid liposomes containing 50 mol% cholesterol. The cholesterol-containing liposomes inhibited leakage to a greater extent than the vesicles incorporating α-tocopherol but the effect of α-tocopherol at equivalent molar proportions was comparable to cholesterol.
authors.affiliation: Department of Biochemistry, King's College London, London, UK. p.quinn@kcl.ac.uk
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quinn
mesh_terms: D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes; D008854:Microscopy, Electron; D044367:Phase Transition; D010713:Phosphatidylcholines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013499:Surface Properties; D014961:X-Ray Diffraction; D024502:alpha-Tocopherol / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; C010942:1,2-distearoyllecithin; D024502:alpha-Tocopherol