LIPOSOMAL AMPHOTERICIN-B IS TOXIC TO FUNGAL CELLS BUT NOT TO MAMMALIAN-CELLS
LIPOSOMAL AMPHOTERICIN-B IS TOXIC TO FUNGAL CELLS BUT NOT TO MAMMALIAN-CELLS
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DOI：
10.1016/0005-2736(84)90135-4
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
JULIANO, RL
中科院分区：
文献类型：
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作者：
MEHTA, R;LOPEZBERESTEIN, G;JULIANO, RL
两性霉素B是一种有效但毒性极强的抗真菌药物。最近已经表明，将两性霉素B掺入多层脂质体中导致小鼠中药物毒性的显著降低，而不损失抗真菌效力。到目前为止，两性霉素B脂质体增强治疗指数的机制基础尚不清楚。然而，在这份报告中，我们表明，在体内的影响可以在体外模拟，其中自由，但不是脂质体两性霉素B导致红细胞裂解，而自由和脂质体药物杀死真菌细胞。这些结果表明，脂质体两性霉素B治疗指数的显著改善主要是由于药物与哺乳动物细胞膜相互作用能力的根本改变，而不是药代动力学或药物分布的改变。
Amphotericin B is an efficacious but extremely toxic anti fungal drug. Recently it has been shown that the incorporation of Amphotericin B in multilamellar liposomes results in a marked reduction in drug toxicity in mice with no loss of anti fungal potency. Until now, the mechanistic basis of the enhanced therapeutic index of liposomal Amphotericin B has been unclear. In this report, however, we show that the in vivo effects can be mimicked in vitro where free but not liposomal Amphotericin B causes lysis of erythrocytes while both free and liposomal drug kill fungal cells. These results suggest that the markedly improved therapeutic index of liposomal Amphotericin B is largely due to a fundamental alteration in the ability of the drug to interact with mammalian cell membranes rather than to alterations in pharmacokinetics or drug distribution.