富含胆固醇的纳米乳剂（LDE）可以在循环中携带化疗药物，并将这些药物集中在肿瘤和炎症组织中。该方法改善了药物的生物分布并降低了毒性。然而，LDE 颗粒的结构稳定性（无论是否含有相关药物）尚未得到广泛研究。本研究的目的是通过小角 X 射线散射（SAXS 和 Ultra SAXS）和动态光散射（DLS）研究水溶液中 LDE 和与紫杉醇、依托泊苷或甲氨蝶呤相关的 LDE 随着时间的推移的结构稳定性。结果表明，在 3 个月的观察期内，LDE 和与这些化疗药物相关的 LDE 具有可重复且稳定的粒径、物理结构和聚集行为。根据 DLS 和 Ultra-SAXS 方法（按预先设定的时间间隔执行）的估计，仅 LDE 的平均粒径约为 100 微米。 LDE-紫杉醇的波长为32nm，LDE-甲氨蝶呤的波长为35nm，LDE-依托泊苷的波长为36nm。 Ultra-SAXS分析显示LDE纳米颗粒呈准球形，SAXS显示颗粒内部的药物分子呈现层状组织。 LDE 与相关 PTX、ETO 或 MTX 的制剂在动物实验以及癌症或心血管疾病患者中成功进行了测试，显示出明显低的毒性、良好的耐受性和可能优越的药理作用。通过加强对这些 LDE 制剂结构方面的了解，我们的结果可能有助于这种新型纳米医学工具的后续临床试验。版权所有 © 2024 Elsevier B.V. 保留所有权利。

Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior   over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32nm, of LDE-paclitaxel was 31nm, of LDE-methotrexate was 35nm and of LDE-etoposide was 36nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.Copyright © 2024 Elsevier B.V. All rights reserved.