Preparation of liposomes composed of supercritical carbon dioxide-philic phospholipids using the rapid expansion of supercritical solution process

Abstract The synthesis of supercritical carbon dioxide-philic phospholipids allowed the vitamin E acetate (VEA) liposomes composed of them to be successfully prepared using the rapid expansion of supercritical solution (RESS) process without any organic solvent. The single-factor analysis and the response surface methodology combined with Box–Behnken design were used to optimize the operation conditions. The results indicated that pressure was the most important factor to the encapsulation efficiency of the liposomes, which was increased with a higher pressure. Temperature and mass ratio also had some effects, while the interaction of the three factors was not significant. The liposomes prepared under the optimal conditions (i.e., temperature of 55.45 °C, pressure of 25.00 MPa, and mass ratio of 6.35:1) showed good stability as well as the slow and continuous release behavior. The encapsulation efficiency, average particle size, PDI, and zeta-potential of the prepared liposomes were 92.84 ± 0.98%, 247.4 ± 6.5 nm, 0.295 ± 0.012, and -42.55 ± 0.64 mV, respectively.