Partitioning of flunitrazepam into model membranes studied by temperature controlled gel filtration chromatography

Abstract

The use of gel filtration chromatography with Sephadex as a separation medium was used in order to study flunitrazepam (FNTZ) partitioning into artificial model membranes consisting of dipalmitoyl-phosphatidylcholine (dpPC) vesicles, under controlled temperature conditions. In this system two phenomena are taking place simultaneously: the ligand–liposome interaction and the lipid self-aggregation to form the liposome. The liposome–FNTZ interaction was evidenced by the non-enantiography of the first derivative of FNTZ elution peak in frontal chromatography through Sephadex G-75. On the other hand, the presence of FNTZ reduced liposomes mean size and increased their size dispersion as evidenced by molecular filtration through Sephadex G-200. The dpPC–buffer FNTZ partition coeficient determined in zonal chromatography through Sephadex G-10 increased about 33% when the temperature rose above the temperature of dpPC transition from the liquid crystalline to the fluid phase. Gel filtration chromatography seems a suitable technique to study lipid liposome–FNTZ interactions at a qualitative level. In addition, this technique has the advantage over other methods of giving the possibility of observing the mutual effects exerted between the drug and the self-aggregating structure. © 1997 John Wiley & Sons, Ltd.