AbstractMycophenolic acid (MPA) is mainly considered an immunosuppressive drug because it is an inhibitor of inosine monophosphate dehydrogenase (IMPDH), and selectively inhibits T- and B-cell proliferation. The aim of this study was to develop the ethosome containing MPA to enhance skin permeation after topical administration for the enhancement of skin permeation after topical administration. In this study, the analysis of MPA was performed using HPLC method. The effects of pH and ethanol contents on MPA solubility were evaluated to find out the suitable dispersion medium for the ethosome preparations. The solubility profiles of MPA were investigated as a function of pH and ethanol content. In addition, the effects of formulation compositions on the physical appearance, entrapment efficiency, zeta potential, particle size and size distribution were investigated. It was found that the ethosome of MPA (10mg/mL) could be prepared by using the thin film hydration method. The optimized formulation composed of 4% w/v SPC:CHOL:Tween80:DA (6:2:1:1 molar ratio) as lipid component and 30% v/v ethanol in phosphate buffer pH 7.4 as dispersion medium. The MPA ethosome gave the vesicular size of 371 ± 8nm (PI = 0.27 ± 0.02nm), the zeta potential of -46 ± 5mV and the entrapment efficiency of 56 ± 1%.