Nanodisks derived from amphotericin B lipid complex.

Nanodisks derived from amphotericin B lipid complex.
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DOI:
10.1002/jps.21325
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发表时间:
2008-10
影响因子:
3.8
通讯作者:
Ryan, Robert O.
Ryan, Robert O.
中科院分区:
医学3区
文献类型:
--
作者:
Tufteland, Megan;Ren, Gang;Ryan, Robert O.

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本研究的目的是确定载脂蛋白对两性霉素B脂质复合物(ABLC)的影响。我们报告,ABLC与重组人载脂蛋白A-I(apoA-I)的孵育诱导ABLC的溶解,通过将微米级磷脂/AMB组件转化为离散的纳米级盘状复合物称为纳米盘(ND)。通过光谱学和电子显微镜监测ApoA-I诱导的ABLC溶解度和形态的变化。在酵母和病原真菌生长抑制测定中评价AMB功效,并在培养的Hep 3B细胞中评估AMB制剂对细胞毒性的影响。与ND相关的AMB比与ABLC相关的AMB更有效地雾化。因此,将ABLC转化为ND保留了AMB的有效生物活性以及ABLC制剂的降低的毒性。ABLC衍生的AMB-ND在稳定性、储存、雾化效率方面比传统ABLC具有优势,并通过对其蛋白质成分进行基因工程为组织特异性靶向提供了内在的“手柄”。
The goal of this study was to determine the effect of apolipoprotiens on Amphotericin B lipid complex (ABLC). We report that incubation of ABLC with recombinant human apolipoprotein A-I (apoA-I) induces solubilization of ABLC by transforming the micron sized phospholipid/AMB assemblies into discrete nanoscale disk-shaped complexes termed nanodisks (ND). ApoA-I induced changes in ABLC solubility and morphology were monitored by spectroscopy and electron microscopy. AMB efficacy was evaluated in yeast and pathogenic fungi growth inhibition assays and the effect of AMB formulation on cell toxicity was assessed in cultured Hep3B cells. AMB associated with ND were more efficiently nebulized than AMB associated with ABLC. Thus, transformation of ABLC into ND preserves the potent biological activity of AMB as well as the reduced toxicity of the ABLC formulation. ABLC derived AMB-ND offer advantages over conventional ABLC in terms of stability, storage, nebulization efficiency and provides an intrinsic “handle” for tissue specific targeting via genetic engineering of its protein component.
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发表时间: 2006-04-01
影响因子: 4.9
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