Non-phospholipid liposomes with high sterol content display a very limited permeability

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We demonstrate that it is possible to form non-phospholipid fluid bilayers in aqueous milieu with a mixture of palmitic acid (PA),cholesterol (Chol),and cholesterol sulfate (Schol) in a molar proportion of 30/28/42.These self-assemblies are shown to be bilayers in the liquid ordered phase.They are stable between pH 5 and 9.Over this pH range,the protonation/deprotonation of PA carboxylic group is observed but this change does not appear to alter the stability of these bilayers,a behavior contrasting with that observed for binary mixtures of PA/Chol,and PA/Schol.The multilamellar dispersions formed spontaneously from the PA/Chol/Schol mixture could be successfully extruded to form Large Unilamellar Vesicles (LUVs).These LUVs show interesting permeability properties,linked with their high sterol content.These non-phospholipid liposomes can sustain a pH gradient (pH internal 8/pH external 6) 100 times longer than LUVs made of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and cholesterol,with a molar ratio of 60/40.Moreover,the non-phospholipid LUVs are shown to protect ascorbic acid from an oxidizing environment (1 mM iron(III)).Once entrapped in liposomes,ascorbic acid displays a degradation rate similar to that obtained in the absence of iron(III).These results show the possibility to form novel nanocontainers from a mixture of a monoalkylated amphiphile and sterols,with a good pH stability and showing interesting permeability properties. We demonstrate that it is possible to form non-phospholipid fluid bilayers in aqueous milieu with a mixture of palmitic acid (PA), cholesterol (Chol), and cholesterol sulfate (Schol) in a molar proportion of 30/28/42. These self -assemblies are shown to be bilayers in the liquid ordered phase. They are stable between pH 5 and 9. Over this pH range, the protonation / deprotonation of PA carboxylic group is observed but this change does not appear to alter the stability of these bilayers , a behavior contrasting with that observed for binary mixtures of PA / Chol, and PA / Schol. The multilamellar dispersions formed spontaneously from the PA / Chol / Schol mixture could be successfully extruded to form Large Unilamellar Vesicles (LUVs). These LUVs show interesting permeability properties, linked with their high sterol content. The non-phospholipid liposomes can sustain a pH gradient (pH internal 8 / pH external 6) 100 times longer than LUVs made of 1-palmitoyl-2-oleoyl-sn- glycero-3- phosphocholine (POPC) and cho lesterol, with a molar ratio of 60 / 40. Moreover, the non-phospholipid LUVs are shown to protect ascorbic acid from an oxidizing environment (1 mM iron (III)). Once entrapped in liposomes, ascorbic acid displays a degradation rate similar to that obtained in the absence of iron (III) .These results show the possibility to form novel nanocontainers from a mixture of a monoalkylated amphiphile and sterols, with a good pH stability and showing interesting permeability properties.
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