Structural characterization of cholesterol-rich nanoemulsion (LDE)

IF 3.4 3区 生物学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Aline S. Perez , Aleksandra T. Morikawa , Raul C. Maranhão , Antônio M. Figueiredo Neto
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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.

Abstract Image

富含胆固醇的纳米乳液(LDE)的结构特征。
富含胆固醇的纳米乳液(LDE)可在血液循环中携带化疗药物,并可将这些药物集中在肿瘤和炎症组织中。这种方法可改善药物的生物分布并降低毒性。然而,对于不含或含有相关药物的 LDE 粒子的结构稳定性,还没有进行广泛的研究。本研究旨在通过小角 X 射线散射(SAXS 和 Ultra SAXS)和动态光散射(DLS)研究 LDE 和与紫杉醇、依托泊苷或甲氨蝶呤相关的 LDE 在水溶液中随时间变化的结构稳定性。结果表明,在 3 个月的观察期内,与这些化疗药物相关的 LDE 和 LDE 具有可重现且稳定的粒径、物理结构和聚集行为。根据 DLS 和 Ultra-SAXS 方法(按预先确定的时间间隔进行)估算,单独使用的 LDE 的平均粒径约为 32 nm,LDE-紫杉醇的平均粒径约为 31 nm,LDE-甲氨蝶呤的平均粒径约为 35 nm,LDE-依托泊苷的平均粒径约为 36 nm。Ultra-SAXS 分析表明,LDE 纳米粒子呈类球形,而 SAXS 则表明,粒子内的药物分子呈层状组织。与 PTX、ETO 或 MTX 相关的 LDE 制剂已成功地在动物实验和癌症或心血管疾病患者中进行了测试,显示出明显的低毒性、良好的耐受性和可能的卓越药理作用。通过加强对这些 LDE 制剂结构方面的了解,我们的研究结果可能有助于这种新型纳米医学工具的后续临床试验。
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来源期刊
Chemistry and Physics of Lipids
Chemistry and Physics of Lipids 生物-生化与分子生物学
CiteScore
7.60
自引率
2.90%
发文量
50
审稿时长
40 days
期刊介绍: Chemistry and Physics of Lipids publishes research papers and review articles on chemical and physical aspects of lipids with primary emphasis on the relationship of these properties to biological functions and to biomedical applications. Accordingly, the journal covers: advances in synthetic and analytical lipid methodology; mass-spectrometry of lipids; chemical and physical characterisation of isolated structures; thermodynamics, phase behaviour, topology and dynamics of lipid assemblies; physicochemical studies into lipid-lipid and lipid-protein interactions in lipoproteins and in natural and model membranes; movement of lipids within, across and between membranes; intracellular lipid transfer; structure-function relationships and the nature of lipid-derived second messengers; chemical, physical and functional alterations of lipids induced by free radicals; enzymatic and non-enzymatic mechanisms of lipid peroxidation in cells, tissues, biofluids; oxidative lipidomics; and the role of lipids in the regulation of membrane-dependent biological processes.
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