The influence of different synthetic lipid mixtures approximating the composition of stratum corneum on the formation and physicochemical properties of liposomes was investigated with the aim of characterizing these structures. To this end, a lipid mixture containing ceramide (40%), cholesterol (25%), palmitic acid (25%) and cholesteryl sulfate (10%) was chosen as a central composition of the optimizing Box and Behnken experimental model for three variables. From these compositions, the optimizing lipid percentage range was varied for each lipid +/-15%, except for the cholesteryl sulfate in which case the variation was extended to +/-100%. Liposomes were prepared by sonication at 63 degrees C in a buffered medium (100 mM NaCl, 5 mM TRIS) at pH 7.5 and supplemented in some cases with 10 mM of 5(6)-carboxyfluorescein. The vesicle size distribution of liposome suspensions (nm) was determined by photon correlation spectrometry, whereas the internal volume (ml per mmol lipid) was determined by spectrofluorometry. Transmission electron microscopy (TEM) reveals the presence of unilamellar liposomes in al the lipid mixtures investigated. With regard to the physicochemical properties of the systems, increasing concentrations of ceramide, palmitic acid and cholesterol (or low cholesteryl sulfate concentrations) result in a decrease in both the size of the vesicles and the internal volume of these structures, This direct correlation confirms the formation of similar bilayer structures in all cases.