PHYSICAL STABILITY OF DIFFERENT LIPOSOME COMPOSITIONS OBTAINED BY EXTRUSION METHOD

Six different liposome compositions were evaluated according their physical stability. The compositions used were (in mole ratio): dipalmitoylphosphatidylcholine (DPPC): DPPC:cholesterol (CHOL) (1:1), DPPC:CHOL (1:6:1), DPPC:CHOL: sphingomyelin (SFM) (7:2:1), DPPC:CHOL: stearylamine (STE) (8:5:1) and DPPC:CHOL: dicetyl phosphate (DCP) (8:5:1). The liposomes were obtained by the extrusion method, through polycarbonate membranes of 0.1 mu m pore size. The captured volume, number of lamellae, size and polydispersity of the vesicle populations were determined for all compositions. The physical stability was checked at -20 degrees C, room temperature, 4 degrees C and 50 degrees C by determining the changes in vesicle size over a maximum of 40 days. The process of aggregation and/or fusion was observed by photon correlation spectroscopy. From the results, we can establish that the above compositions are metastable at a temperature of 50 degrees C. On the other hand, values of captured volume were smaller than predicted by theory. This fact can be explained by the non-sphericity of extruded vesicles. In relation to the stability, the introduction of CHOL in the formulation allows keeping the vesicles at 4 degrees C. In contrast, liposomes containing only DPPC are very stable at room temperature. Compositions with a high stability are those that have present SFM or STE. The latter keeps the structural bilayer at temperatures < 0 degrees C without cryoprotectors. Both the lipids, STE and DCP, form vesicles with a higher number of lamellae.