Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study.
Small-Angle X-ray Scattering for PEGylated Liposomal Doxorubicin Drugs: An Analytical Model Comparison Study.
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聚乙二醇化阿霉素脂质体药物的小角X射线散射：分析模型比较研究。
DOI：
10.1021/acs.molpharmaceut.3c00396
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发表时间：
2023-08
影响因子：
4.9
通讯作者：
Yiwen Li;Jianqiao Zhang;Panqi Song;Xiaran Miao;Guangfeng Liu;Chunming Yang;Xiaohui Wei;Na Li;Fenggang Bian
中科院分区：
文献类型：
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作者：
Yiwen Li;Jianqiao Zhang;Panqi Song;Xiaran Miao;Guangfeng Liu;Chunming Yang;Xiaohui Wei;Na Li;Fenggang Bian
脂质体给药系统被认为是高效、安全的化疗药物平台，其中阿霉素脂质体是最具代表性的纳米药物。以高空间和时间分辨率表征脂质体纳米药物的结构对于分析和评估其稳定性和有效性至关重要。小角X射线散射（SAXS）是一个强大的工具，越来越多地用于研究脂质体传递系统。在这项研究中，我们选择了一个Doxil样的聚乙二醇脂质体阿霉素（PLD）作为一个例子，其特征在于脂质体药物的结构，使用同步加速器SAXS。经典的分析模型，包括球壳或平板几何形状与高斯或均匀的电子密度分布，被用来模拟脂质体膜的内部结构。采用圆柱体模型拟合药物晶体在脂质体中的散射。使用这些分析模型表征了原始药物Caelyx和我们实验室制备的类似研究药物的高分辨率结构。进一步比较了脂质体膜的厚度和药物晶体的形态等结构参数。结果表明，在一定的散射矢量范围内，具有高斯电子密度分布的球壳结构和平板结构都适合描述脂质体膜的结构特征，而具有均匀电子密度分布的模型拟合效果较差.这项研究突出了SAXS的技术特点，它提供了脂质体药物在纳米级的结构信息。该方法简便、可靠，可用于脂质体药物的结构分析，有助于小角X射线散射技术在纳米药物生产和调控中的广泛应用。
Liposomal delivery systems are recognized as efficient and safe platforms for chemotherapeutic agents, with doxorubicin-loaded liposomes being the most representative nanopharmaceuticals. Characterizing the structure of liposomal nanomedicines in high spatial and temporal resolution is critical to analyze and evaluate their stability and efficacy. Small-angle X-ray scattering (SAXS) is a powerful tool increasingly used to investigate liposomal delivery systems. In this study, we chose a Doxil-like PEGylated liposomal doxorubicin (PLD) as an example and characterized the liposomal drug structure using synchrotron SAXS. Classical analytical models, including the spherical-shell or flat-slab geometries with Gaussian or uniform electron density profiles, were used to model the internal structure of the liposomal membrane. A cylinder model was applied to fit the scattering from the drug crystal loaded in the liposomes. The high-resolution structures of the original drug, Caelyx, and a similar research drug prepared in our laboratory were characterized using these analytical models. The structural parameters of PLDs, including the thickness of the liposomal membrane and morphology of the drug crystal, were further compared. The results demonstrated that both spherical-shell and flat-slab geometries with Gaussian electron density distribution were suitable to elucidate the structural features of the liposomal membrane under a certain range of scattering vectors, while models with uniform electron density distribution exhibited poor fitting performance. This study highlights the technical features of SAXS, which provides structural information at the nanoscale for liposomal drugs. The demonstrated methods are reliable and easy-to-use for the structural analysis of liposomal drugs, which are helpful for a broader application of SAXS in the production and regulation of nanopharmaceuticals.