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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:反离子和辅助脂质含量在纳米载波系统的设计与性质中的作用:2D和3D脂质组装中的生物物理研究

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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:纳米载波系统的物理化学特性及其生物学性能之间存在直接相关性,包括在生理条件下的稳定性,细胞内化和转染效率。因此,了解影响自组装纳米载体的生物物理方面是有效配方的理性设计的决定因素。在本研究中,制备了对由阳离子脂质脱芝二二甲基溴化铵和氯化物(DoDab和DoDAC)形成的每种组分对分子组织的影响的综合评价,并进行中性脂质单烯醇(MO)。具体地,通过Langmuir表面压力 - 分子面积(π-a)等温,Brewster角度显微镜(BAM)在2D和3D组件中评价辅助脂质含量(Mo)和阳离子脂质的反离子的作用。 ),红外反射吸收光谱(Irras),共聚焦拉曼显微镜和小角度X射线散射(萨克斯)。结果表明,Mo在DoDAC和Dodab双层的不同分布,以及依赖于Mo含量的流化效果。对于低Mo摩尔比,流化效果在DoDAC中更加明显?:Mo混合物,表明Dodab在DoDab双层中更均匀地分布Mo。对于高Mo摩尔比,膜的封装对于阳离子脂质相似,并且抗衡离子的效果衰减。两个阳离子系统中的Mo的分布与筛选带电组中的反离子的效率密切相关。

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