Liposomal formulations of cyclosporin A have been investigated in a series of studies. One of the most used arguments for the development of this pharmaceutical preparation was the high lipophilicity of cyclosporin A, which ensures an encapsulation of cyclosporin A in the liposomal bilayer. From this study on the interaction of cyclosporin with lipids spread as a monolayer on the air/water interface we demonstrate, that one molecule of cyclosporin A occupies an area of 260 Å2 in the lipid monolayer. These data correlate well with molecular modelling data, calculating a cross-sectional area of 230 Å2 for a cyclosporin A molecule. Calculation of a partition coefficient using these data at different surface pressures results in a value of about 4000 at a surface pressure of about 31 mN/m. This partition coefficient is also found in bilayer membranes supporting the notion, that phospholipid bilayer systems have a surface pressure of about 32 mN/m. If the lipid:cyclosporin A ratio exceeds a value of 20, the lipid monolayer becomes nonlinear. Cyclosporin A starts to detoriate liposomal membranes at similar lipid:cyclosporin ratios. It could also be concluded from our measurements at the air/water interface, that cyclosporin A is able to exchange binding places between membranes rapidly with a time constant of about 2.5 min. Lipid monolayer experiments are not only an easy and fast method to obtain information about molecule interactions with lipid membranes, but is also a suitable method to develop liposomal formulations of drugs.
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