Affinity of amphotericin B for phosphatidylcholine vesicles as a determinant of the in vitro cellular toxicity of liposomal preparations.
Affinity of amphotericin B for phosphatidylcholine vesicles as a determinant of the in vitro cellular toxicity of liposomal preparations.
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两性霉素 B 对磷脂酰胆碱囊泡的亲和力是脂质体制剂体外细胞毒性的决定因素。
DOI：
10.1016/0005-2736(90)90381-w
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Bolard,J
中科院分区：
文献类型：
--
作者：
Jullien,S;Brajtburg,J;Bolard,J
用两性霉素B （AmB）脂质体与不饱和脂肪酸酰基链磷脂酰胆碱（卵黄PC）组成的单层小囊泡（SUV）孵育获得两性霉素B (AmB)，对白色念珠菌和人红细胞进行处理。细胞效应是通过细胞内部K+含量的变化和真菌细胞形成的菌落数量的变化来确定的，或者通过红细胞血红蛋白潴留的减少来测量溶血。通过两种方法获得剂量-响应曲线：在所用AmB浓度范围内保持AmB与磷脂的比例恒定（R= 10−2），或在磷脂浓度恒定（C= 0.2 mM）时改变AmB的浓度。脂质体制剂AmB对真菌的活性与二甲亚砜中AmB的活性相同，但对红细胞的活性（内部K+改变）或活性（溶血）较低。另一方面，在用于细胞研究的两种条件下，通过圆二色性、荧光和紫外线吸收来监测AmB与SUV的结合，作为AmB浓度的函数。抗生素总浓度为2·10−7M时，AmB的结合量很低，但随着浓度的增加而增加，10−5M时达到90%。在我们使用的所有试验中，抗细胞作用可归因于游离的AmB水平（未与脂质结合）。因此，这些水平随AmB总浓度的变化可以解释与作为二甲亚砜溶液添加的AmB相比，脂质体AmB对真菌和红细胞毒性的选择性增加。事实上，真菌细胞对二甲亚砜中低浓度的AmB敏感；在这些浓度下，在脂质体制剂中，AmB不与磷脂结合，因此与添加在二甲亚砜中一样具有活性。相比之下，红细胞只对二甲亚砜中高浓度的AmB敏感；在这些浓度下，AmB几乎完全与磷脂结合，因此活性低得多。
Candida albicansand human erythrocytes were treated with liposomal amphotericin B (AmB) obtained by incubation of free AmB with small unilamellar vesicles (SUV) composed of unsaturated fatty acyl chains phosphatidylcholine (egg-yolk PC). Cellular effects were determined by changes in the K+internal content of cells and in the number of colonies formed by fungal cells or as hemolysis, measured as a decrease i haemoglobin retention by erythrocytes. Dose-response curves were obtained by two procedures: either the ratio of AmB to phospholipids was kept constant over the AmB concentration range used (R= 10−2) or the phospholipid concentration was kept constant (C= 0.2 mM) and the concentration of AmB varied. The liposomal preparations of AmB were as active against fungi as AmB in dimethylsulfoxide but less active (internal K+changes) or inactive (hemolysis) against erythrocytes. On the other hand the binding of AmB to the SUV, as a function of the AmB concentration, was monitored by circular dichroism, fluorescence and UV absorption, in the two conditions used for the cellular studies. The amount of AmB bound when the total concentration of antibiotic was 2 · 10−7M was very low but increased with concentration and reached 90% at 10−5M. In all the assays we used, the anticellular effects could be attributed to the levels of AmB remaining free (unbound to the lipids). The variations of these levels with total AmB concentration could therefore explain the increased selectivity of liposomal AmB in toxicity against fungi and erythrocytes as compared to that of AmB added as a solution in dimethylsulfoxide. Indeed fungal cells are sensitive to low concentrations of AmB in dimethylsulfoxide; at these concentrations, in liposomal preparations, AmB is not bound to phospolipids and therefore as active as if added in dimethylsulfoxide. By contrast erythrocytes are only sensitive to much higher concentrations of AmB in dimethylsulfoxide; at these concentrations AmB is almost totally bound to phospholipids and therefore much less active.
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影响因子：
2.9
作者：
ERNST, C;GRANGE, J;DUPONT, G
通讯作者：
DUPONT, G
双放射性标记的两性霉素 B 甲酯和两性霉素 B 在非人类灵长类动物猕猴中的分布。
DOI：
10.1093/jac/6.2.241
发表时间：
1980
期刊：
The Journal of antimicrobial chemotherapy
影响因子：
--
作者：
Ruth M. Lawrence;Paul D. Hoeprich;Franklyn A. Jagdis;Nobuo Monji;A. C. Huston;Carl P. Schaffner
通讯作者：
Carl P. Schaffner
多烯抗生素与磷脂酰胆碱/甾醇囊泡复合物的解离动力学和平衡结合特性。
影响因子：
2.9
作者：
Witzke,NM;Bittman,R
通讯作者：
Bittman,R
影响因子：
2.9
作者：
G. C. Newman;C. Huang
通讯作者：
G. C. Newman;C. Huang
两性霉素 B 及其 N-果糖基衍生物与小鼠胸腺细胞的相互作用：使用荧光膜探针的比较研究。
DOI：
--
发表时间：
1989
期刊：
Biochimica et Biophysica Acta
影响因子：
--
作者：
N. Henry;Michel Seman;Jacques Bolard
通讯作者：
Jacques Bolard