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Role of counter-ion and helper lipid content in the design and properties of nanocarrier systems: a biophysical study in 2D and 3D lipid assemblies

机译:抗衡离子和辅助脂质含量在纳米载体系统设计和特性中的作用:2D和3D脂质组装体的生物物理研究

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摘要

There is a direct correlation between the physicochemical properties of nanocarrier systems and their biological performance, including stability under physiological conditions, cellular internalization and transfection efficiency. Therefore, understanding the biophysical aspects that affect self-assembled nanocarriers is determinant for a rational design of efficient formulations. In this study, a comprehensive evaluation of the effects of each component on the molecular organization of aggregates formed by the cationic lipids dioctadecyldimethylammonium bromide and chloride (DODAB and DODAC) and the neutral lipid monoolein (MO) was made. Specifically, the effects of the helper lipid content (MO) and the role of the counter-ion of the cationic lipids were evaluated in 2D and 3D assemblies by Langmuir surface pressure–molecular area (π–A) isotherms, Brewster Angle Microscopy (BAM), infrared reflection absorption spectroscopy (IRRAS), confocal Raman microscopy, and Small Angle X-ray Scattering (SAXS). The results show that MO has a different distribution on the DODAC and DODAB bilayers, and a fluidizing effect dependent on the MO content. For low MO molar ratios, the fluidizing effect was more pronounced in DODAC : MO mixtures, indicating a more homogeneous distribution of MO in DODAC than in DODAB bilayers. For high MO molar ratios, packing of membranes was similar for both cationic lipids, and the effect of the counter-ion is attenuated. The distribution of MO in the two cationic systems is closely related with the efficiency of the counter-ions in the screening of the charged group.
机译:纳米载体系统的理化性质与其生物学性能之间存在直接的相关性,包括在生理条件下的稳定性,细胞内在化和转染效率。因此,了解影响自组装纳米载体的生物物理方面是合理设计有效制剂的决定性因素。在这项研究中,对每种成分对由阳离子脂质二十八烷基二甲基溴化铵和氯化物(DODAB和DODAC)以及中性脂质单油精(MO)形成的聚集体的分子组织的影响进行了综合评估。具体而言,通过Langmuir表面压力-分子面积(π-A)等温线,布鲁斯特角显微镜(BAM)在2D和3D组件中评估了辅助脂质含量(MO)的影响和阳离子脂质的抗衡离子的作用。 ),红外反射吸收光谱(IRRAS),共焦拉曼显微镜和小角X射线散射(SAXS)。结果表明,MO在DODAC和DODAB双层膜上具有不同的分布,并且流化效果取决于MO含量。对于低摩尔摩尔比,流化作用在DODAC:MO混合物中更为明显,表明在DODAC中MO的分布比在DODAB双层中更均匀。对于高MO摩尔比,两种阳离子脂质的膜堆积相似,并且抗衡离子的作用减弱。 MO在两个阳离子体系中的分布与带电基团筛选中抗衡离子的效率密切相关。

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