Phase behaviour of amphotericin B multilamellar vesicles.
Phase behaviour of amphotericin B multilamellar vesicles.
复制标题
两性霉素 B 多层囊泡的相行为。
DOI：
10.1016/0005-2736(91)90396-p
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
C. Grant
中科院分区：
文献类型：
--
作者：
K. Hamilton;K. R. Barber;J. Davis;K. Neil;C. Grant
由于脂质体阿替西霉素B的副作用特征和关键物理性质反映了水合制剂的分子性质，因此一直致力于理解这种性质。我们在这里描述的差示扫描量热法检查的主要转变的区域的相行为的阿替西霉素B多层脂质体用于investigationally患者治疗。脂质体由7：3二肉豆蔻酰磷脂酰胆碱/二肉豆蔻酰磷脂酰甘油（7：3 DMPC/DMPG）组成，含有高达33 mol%的药物。用纯DMPC或纯1-油酰-2-硬脂酰磷脂酰胆碱（OSPC）代替7：3 DMPC/DMPG的制剂进行相同的测量以进行比较。DSC衍生的部分相图类似于先前使用EPR光谱法记录的含有阿替霉素B的7：3 DMPC/DMPG的未经超声处理的脂质体以及具有不同纯饱和和不饱和磷脂酰胆碱的混合物的部分相图（Grant，C.W.M.，等人（1989）Biochim. Biophys. Acta 984，11-20）。与完成温度相比，脂质体宿主基质的流化起始温度相对不受药物影响。这种效应对于不饱和磷脂基质特别显著。部分相图被解释为表明，阿替霉素B具有在膜内分离成刚性相的趋势。这与分子建模的考虑是一致的，其表明阿替霉素B可能作为低聚物存在于磷脂基质中。所研究的磷脂双层的DSC熔融曲线的药物诱导的改变不如对7：3 DMPC/DMPG的部分超声处理制剂报道的那些广泛（Janoff，A.S.，等人（1989）Proc.Natl. Acad. Sci. USA 85，6122-6126）。进一步孵育样品后，获得的熔融曲线未发生变化，表明水合制剂代表药物稳定形式。
Because side effect profiles and key physical properties of liposomal amphotericin B reflect the molecular nature of the hydrated preparations, effort has been directed toward understanding this nature. We describe here an examination by differential scanning calorimetry in the region of the main transition of the phase behaviour of amphotericin B multilamellar liposomes used investigationally for patient treatment. Liposomes were composed of 7:3 dimyristoylphosphatidylcholine/dimyristoylphosphatidylglycerol (7:3 DMPC/DMPG) containing up to 33 mol% drug. Preparations in which pure DMPC or pure 1-oleoyl-2-stearoylphosphatidylcholine (OSPC) was substituted for 7:3 DMPC/DMPG were subjected to the same measurements for comparison. The DSC-derived partial phase diagrams were similar to those previously recorded using EPR spectroscopy for unsonicated liposomes of 7:3 DMPC/DMPG containing amphotericin B, and for mixtureswith different pure saturated and unsaturated phosphatidylcholines (Grant, C.W.M., et al. (1989) Biochim. Biophys. Acta 984, 11–20). Fluidization onset temperatures for liposome host matrices were relatively unaffected by drug compared to the temperatures of completion. This effect was particularly marked for the unsaturated phospholipid matrix. Partial phase diagrams were interpreted as demonstrating that amphotericin B has a tendency to separate into a rigid phase within the membrane. This is consistent with molecular modelling considerations which suggest that amphotericin B may exist as oligomers in a phospholipid matrix. Drug-induced alterations of DSC melting profiles for the phospholipid bilayers studied were less extensive than those reported for partially sonicated preparations of 7:3 DMPC/DMPG (Janoff, A.S., et al. (1989) Proc. Natl. Acad. Sci. USA 85, 6122–6126). Melting profiles obtained did not change upon further sample incubation, suggesting that the hydrated preparation represented a thermodynamically stable form.
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
用于测定两性霉素 B 与脂质体结合的圆二色性。
影响因子：
2.9
作者：
Jullien,S;Vertut-Croquin,A;Brajtburg,J;Bolard,J
通讯作者：
Bolard,J
两性霉素 B 选择性胆固醇依赖性诱导磷脂囊泡中的 H/OH-电流。
影响因子：
2.9
作者：
Hartsel,SC;Perkins,WR;McGarvey,GJ;Cafiso,DS
通讯作者：
Cafiso,DS