Study of the sedimentation behaviour of liposomal drug delivery system

Abstract

The sedimentation behaviour of liposomal dispersions was investigated in order to determine the effect of both the lipid composition and the drug concentration on the surface properties of liposomes. In the sedimentation experiments equal amounts of liposomes are allowed to settle in binary liquid mixtures of different surface tensions. It was found that the sedimentation volume, V sed, of liposomes changed with varying surface tension, γ LV, of the suspending liquids. A minimum (or a maximum ) occurred in V sed when the surface tension of the liquid medium was equal to that of the liposome “particles”, i.e. when γ LV=γ PV. Consequently, the surface tension of liposomes, γ PV, may be identified by determining the liquid surface tension, γ LV, at which the V sed shows an extremum. The sedimentation volume of various multilamellar (MLV) liposome preparations formulated from soylecithins and cholesterol was measured in n-propanol/water binary liquid mixtures. Liposomal dispersions with different compositions were prepared in distilled water. Econazole nitrate, an antifungal agent, served as model drug. Results indicated that the surface tension of liposomes directly relates to the phospholipid and cholesterol molar ratio and is also affected by the drug concentration. The surface tension of liposomes decreases with increasing cholesterol concentration in the lipid bilayer. An increase in the drug concentration, without changing the lipid concentration, resulted in an increase of the surface tension of liposomes. It was also found that the sedimentation volume experiments performed with selected liposome samples yielded essentially the same “particle” surface tensions, γ PV, as when the surface tensions of those liposomes were determined by axisymmetric drop shape analysis (ADSA).