Amphotericin B가 함유된 Egg PC 리포솜의 용혈 특성

Abstract

The hemolytic characteristics of amphotericin B-containing liposomes have been investigated in vitro. From the hemolysis of human erythrocytes against free and liposomal amphotericin B, the marked reduction in the toxicity of amphotericin B was observed by incorporating the drug in egg PC liposomes. For 45 min, free amphotericin B at $9.6\;{\mu}g/ml$ could completely lyse 2 wt% human erythrocytes. However, liposomal amphotericin B had essentially no lytic effect even in the range over $9.6\;{\mu}g/ml$. In the 66 hr-hemolysis experiment, liposomal amphotericin B showed the slowly hemolysing chracteristics during the experimental period regardless of the concentration of amphotericin B but rapid hemolysis only for 12 hr was observed in the case of free amphotericin B and the degree of hemolysis for 12 hr was maintained after that time. Also the hemolysing ability of liposomal amphotericin B at $4\;{\mu}g/ml$ was lower than that of free amphotericin B at the same concentration for 66 hr. On the other hand, the dependence of hemolysis on amphotericin B contents in egg PC liposomes was significant between 1.64 mole% amphotericin B-containing liposomes and 15.79 or 27.27 mole% amphotericin B-containing liposomes. But no marked difference in hemolysis was observed between 15.79 and 27.27 mole% amphotericin B-containing liposomes. Especially, cholesterol as an excipient in amphotericin B-containing liposomes significantly reduced the hemolysis of human erythrocyte. The degree of hemolysis in 5 mole% amphotericin B-containing liposomes was reduced to approximately 50% of value in the cholesterol-free liposomes by adding 50% cholesterol.