Anticellular activity and temperature - sensitive release of target : selective liposomes

Abstract

Until now, amphotericin B (AmB)-containing liposomes have been prepared by film swelling method. The liposomal AmB was less toxic than free AmB in vivo and in vitro. However, the toxicity of the liposomal AmB prepared by film swelling method is still high and should be reduced. Another problem, involved in the method, to be overcome is storage stability in buffer solution. The physical instability of liposomes, aggregation or fusion, may alter the inherent natures including size, lamellarity and assembling state of lipids, leading to the undesirable release of entrapped drugs. To overcome these shortcoming, two novel methods for the preparation of AmB-containing liposomes were designed. One is precipitation method and the other is spray drying. The liposomes containing AmB prepared by conventional film swelling method and precipitation method were investigated in terms of structure, stabilities and anticellular activities. The structure of liposomes were investigated with transmission electron micrograph, circular dichroism and X-ray diffraction. The stabilities of liposomes were studied in terms of release of AmB. Finally, the anti-cellular activities of the liposomal AmB were illuminated in view of the structure and the release of AmB. The liposomes prepared by spray drying method also were investigated in terms of size and anticellular activities. The liposomes containing AmB prepared by film swelling method exhibit much lower hemolytic abilities than free AmB. This is probably because of the presence of a non-toxic form of AmB-phospholipid complex. The presence of AmB-phospholipid complex in this formulation was confirmed by positive CD peak around 330 nm. This indicates that in egg PC/AmB/water system, AmB-phospholipid complex and AmB-containing liposomes would coexist. According to the result of DLS, a higher complexation give the particles of smaller size. With assay for AmB and phospholipid, the complex was AmB-rich and the liposome was AmB-poor. The ...