The physical characteristics of egg PC liposomes were studied such as the membrane permeability, the solubilization by bile salt, the phase transition, the size distribution, and the degree of aggregation, and the hemolytic characteristics of liposomal amphotericin B were investigated with lysis of human erythrocytes in vitro. The size distributions of amphotericin B-containing liposomes were determined by a DLS method. The effective size of liposomes increased as cholesterol contents increased, but amphotericin B influenced their size reduction. The release rate of calcein encapsulated in 3 mole% amphotericin B-containing liposomes was lower than that of pure egg PC liposomes. The absorbance change and cacein release by DOC from 5 mole% amphotericin B-containing liposomes were more moderate than in the case of pure egg PC liposomes. Therefore, amphotericin B would be accumulated into the membranes, reforming the structure and the transport.
The phase transition temperatures of 5 mole% amphotericin B-containing DPPC liposomes were calorimetrically determined, resulting in two distinct peaks, one for DPPC liposome and the other for packing-ill amphotericin B-phospholipid complex. The increase of cholesterol contents in 5 mole% amphotericin B-containing liposomes results in the rapid aggregation of liposome particles.
From the hemolysis of human erythrocytes in vitro, the marked reduction in the toxicity of amphotericin B was observed by incorporating the drug in egg PC liposomes. For 45min, free amphotericin B at 9.6 μg/ml could completely lyse human erythrocytes. However, liposoml amphotericin B had essentially no lytic effect even in the range over 9.6 μg/ml. On the other hand, cholesterol as exipient in amphotericin B-containing liposomes significantly reduced the hemolysis of human erythrocytes.
