Neutron Scattering Studies of the Effects of Formulating Amphotericin B with Cholesteryl Sulfate on the Drug's Interactions with Phospholipid and Phospholipid-Sterol Membranes.
Neutron Scattering Studies of the Effects of Formulating Amphotericin B with Cholesteryl Sulfate on the Drug's Interactions with Phospholipid and Phospholipid-Sterol Membranes.
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两性霉素 B 与胆固醇硫酸盐配制对药物与磷脂和磷脂甾醇膜相互作用影响的中子散射研究。
DOI：
10.1021/acs.langmuir.5b01365
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Foglia F
中科院分区：
文献类型：
--
作者：
Foglia F
Langmuir表面压力、小角中子散射（SANS）和中子反射率（NR）研究确定了抗真菌药物两性霉素B （AmB）与硫酸胆固醇钠（SCS）（如Amphotec）的配方如何影响其与含麦角甾醇（模型真菌细胞）和含胆固醇（模型哺乳动物细胞）膜的相互作用。以1:1的摩尔比将AmB与硫酸胆固醇混合（产生AmB- scs胶束）的效果与自由的AmB进行了比较，使用由棕榈酰磷脂酰胆碱（POPC）形成的单层和双层，在没有和存在30 mol %麦角甾醇或胆固醇的情况下，在所有情况下使用1:0.05的脂质：AmB的摩尔比。对（双层）SANS和（单层）NR数据的分析表明，游离AmB和AmB- scs在无甾醇和含甾醇膜上引起的膜结构平衡变化是相同的。然而，停止流动的SANS实验显示，暴露于AmB-SCS比暴露于游离药物后囊泡膜的结构变化要快得多，这些变化的动力学随膜组成而变化。对于POPC囊泡，AmB-SCS诱导的结构变化仅在几分钟后就变得明显，并在约30分钟后达到平衡。然而，popc -麦角甾醇和popc -胆固醇囊泡的相应变化发生在~ 5秒内，分别在10秒和120秒后达到平衡。因此，通过配制AmB- scs，增加了AmB插入popc -固醇膜的速率。此外，单层表面压力和SANS结构改变平衡时间的差异表明，在插入后，这些膜内的AmB发生了显著的重排。popc -麦角甾醇与popc -胆固醇系统的平衡时间缩短与AmB对这两种甾醇的已知亲和力差异一致，AmB- scs与popc -麦角甾醇膜相互作用的平衡时间缩短与游离AmB的平衡时间缩短与Amphotec降低宿主毒性一致。
Langmuir surface pressure, small-angle neutron scattering (SANS), and neutron reflectivity (NR) studies have been performed to determine how formulation of the antifungal drug amphotericin B (AmB), with sodium cholesteryl sulfate (SCS)as in Amphotecaffects its interactions with ergosterol-containing (model fungal cell) and cholesterol-containing (model mammalian cell) membranes. The effects of mixing AmB in 1:1 molar ratio with cholesteryl sulfate (yielding AmB-SCS micelles) are compared against those of free AmB, using monolayers and bilayers formed from palmitoyloleoylphosphatidylcholine (POPC) in the absence and presence of 30 mol % ergosterol or cholesterol, in all cases employing a 1:0.05 molar ratio of lipid:AmB. Analyses of the (bilayer) SANS and (monolayer) NR data indicate that the equilibrium changes in membrane structure induced in sterol-free and sterol-containing membranes are the same for free AmB and AmB-SCS. Stopped-flow SANS experiments, however, reveal that the structural changes to vesicle membranes occur far more rapidly following exposure to AmB-SCS vs free drug, with the kinetics of these changes varying with membrane composition. With POPC vesicles, the structural changes induced by AmB-SCS become apparent only after several minutes, and equilibrium is reached after ∼30 min. The corresponding onset of changes in POPC-ergosterol and POPC-cholesterol vesicles, however, occurs within ∼5 s, with equilibrium reached after 10 and 120 s, respectively. The rate of insertion of AmB into POPC-sterol membranes is thus increased through formulation as AmB-SCS. Moreover, the differences in monolayer surface pressure and SANS structure-change equilibration times suggest significant rearrangement of AmB within these membranes following insertion. The reduced times to equilibrium for the POPC-ergosterol vs POPC-cholesterol systems are consistent with the known differences in affinity of AmB for these two sterols, and the reduced time to equilibrium for AmB-SCS interaction with POPC-ergosterol membranes vs that for free AmB is consistent with the reduced host toxicity of Amphotec.
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两性霉素 B 脂质复合物 (Ablc™)：减弱两性霉素 B 相关毒性的分子原理
DOI：
--
发表时间：
1993
期刊：
影响因子：
--
作者：
A. Janoff;W. Perkins;S. Saletan;C. Swenson
通讯作者：
C. Swenson
影响因子：
3.4
作者：
Foglia, F.;Drake, A. F.;Barlow, D. J.
通讯作者：
Barlow, D. J.
在 POPC 空气-水单层和溶液双层系统中研究的长寿命两亲荧光探针。
影响因子：
3.4
作者：
G. Gramlich;J. Zhang;M. Winterhalter;W. Nau
通讯作者：
W. Nau
抗真菌靶点和药物开发的最新进展。
影响因子：
4.1
作者：
S. Sundriyal;Rohit Sharma;R. Jain
通讯作者：
R. Jain
影响因子：
3.4
作者：
NEZIL, FA;BLOOM, M
通讯作者：
BLOOM, M