Selective partitioning of cholesterol and a model drug into liposomes of varying size |
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Authors: | Decker Christiane Fahr Alfred Kuntsche Judith May Sylvio |
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Institution: | 1. Friedrich Schiller University Jena, Department of Pharmaceutical Technology, Lessingstraße 8, D-07743 Jena, Germany;2. Martin Luther University Halle-Wittenberg, Department of Pharmaceutical Technology and Biopharmaceutics, Wolfgang-Langenbeck-Straße 4, D-06120 Halle/Saale, Germany;3. North Dakota State University, Department of Physics, Fargo, ND 58108-6050, USA |
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Abstract: | The resistance of a lipid bilayer with respect to a bending deformation generally depends on the presence of membrane additives such as sterols, cosurfactants, peptides, and drugs. As a consequence, the partitioning of membrane additives into liposomes becomes selective with respect to liposome size; i.e., membrane rigidification depletes the membrane additives in the smaller (more strongly curved) liposomes. We have measured this liposome size-selective partitioning for two membrane additives - cholesterol and the porphyrin-based photosensitizer temoporfin - using asymmetrical flow field-flow fractionation (AF4) of liposomes and radioactive labeling of the membrane additive and lipid. The method yields either the molar cholesterol-to-lipid or the temoporfin-to-lipid ratio as a function of liposome size, from which we calculate the corresponding change of the membrane bending stiffness. For small unilamellar fluid-phase liposomes composed of palmitoyloleoylphosphatidylcholine (POPC) and palmitoyloleoylphosphatidylglycerol (POPG), we find that cholesterol rigidifies the host membrane in a manner consistent with previously reported measurements. In contrast, temoporfin softens this membrane. Partitioning results for gel-phase liposomes composed of dipalmitoylphosphatidylcholine (DPPC) and dipalmitoylphosphatidylglycerol (DPPG) are also curvature-sensitive but cannot be interpreted on the basis of the bending stiffness alone. |
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