Abstract：
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. 32 nm, of LDE-paclitaxel was 31 nm, of LDE-methotrexate was 35 nm and of LDE-etoposide was 36 nm. 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.
摘要：
富含胆固醇的纳米乳剂(LDE)可以在循环中携带化疗剂,并且可以将这些药剂浓缩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，没有或有相关药物，没有被广泛调查。本研究的目的是研究LDE和LDE与紫杉醇相关的结构稳定性。通过小角度X射线散射（SAXS和UltraSAXS）和动态光散射（DLS）在水溶液中的依托泊苷或甲氨蝶呤随时间的变化。结果表明，与这些化疗药物相关的LDE和LDE具有可重复且稳定的粒径，物理结构，以及3个月观察期内的聚集行为。根据DLS和Ultra-SAXS方法估计，以预先设定的间隔进行，单独的LDE的平均粒径约为。32nm，LDE-紫杉醇为31nm，LDE-甲氨蝶呤的浓度为35nm，LDE-依托泊苷的浓度为36nm。Ultra-SAXS分析表明,LDE纳米粒子为准球形,SAXS显示颗粒内的药物分子呈层状组织。LDE与相关PTX的配方，ETO或MTX在动物实验和癌症或心血管疾病患者中成功测试，表现出明显的低毒性，良好的耐受性和可能优越的药理作用。我们的结果可能对这种新型纳米医学工具的后续临床试验有用，通过加强对这些LDE配方的结构方面的了解。
