Liposomes as cyclosporin a carriers: The influence of ordering of hydrocarbon chains of phosphatidylglycerol liposomes on the association with and topography of cyclosporin A

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The addition of cholesterol and stearylamine to liposomes prepared from phosphatidylglycerol containing saturated and unsaturated fatty acids was studied to determine the effect on binding of cyclosporin A (CsA). It was found that liposomes containing phosphatidylglycerol-stearylamine-cholesterol in the molar ratio of 7:2.25:2 had the highest capacity to bind CsA (36.7 mol of phospholipid to 1 mol of CsA), while binding of CsA to phosphatidylglycerol liposomes, phosphatidylglycerol-stearylamine liposomes, or phosphatidylglycerolcholesterol liposomes was significantly lower (342.9, 174.4 and 422.3 mol of phospholipid to 1 mol of CsA, respectively). The binding of CsA to all these liposomes was compared with their order parameters, obtained by electron spin resonance spectroscopy using 5-nitroxide stearic acid spin probe. It was found that increased binding of CsA paralleled the increased ordering of hydrocarbon chains achieved by addition of cholesterol to these liposomes. When liposomes were prepared from pure dimyristoylphosphatidylglycerol (DMPG), 30.7 mol of DMPG were required to bind 1 mol of CsA. The topography of CsA in phosphatidylglycerol liposomes was established by using 5-nitroxide stearic acid as a spin probe. In DMPG liposomes, CsA was found in hydrocarbon chains adjacent to the polar head group, while in liposomes prepared from phosphatidylglycerol containing mixed fatty acids, CsA was associated with the polar head group region without penetrating the hydrocarbon chains of phosphatidylglycerol.