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Doxorubicin Hydrochloride-Loaded Nonionic Surfactant Vesicles to Treat Metastatic and Non-Metastatic Breast Cancer
ACS Omega ( IF 3.7 ) Pub Date : 2021-01-22 , DOI: 10.1021/acsomega.0c05350
Martina Di Francesco 1, 2 , Christian Celia 3 , Maria Chiara Cristiano 4 , Nicola d'Avanzo 1, 3 , Barbara Ruozi 5 , Constantin Mircioiu 6 , Donato Cosco 1 , Luisa Di Marzio 3 , Massimo Fresta 1
Affiliation  

Doxorubicin hydrochloride (DOX) is currently used to treat orthotropic and metastatic breast cancer. Because of its side effects, the use of DOX in cancer patients is sometimes limited; for this reason, several scientists tried designing drug delivery systems which can improve drug therapeutic efficacy and decrease its side effects. In this study, we designed, prepared, and physiochemically characterized nonionic surfactant vesicles (NSVs) which are obtained by self-assembling different combinations of hydrophilic (Tween 20) and hydrophobic (Span 20) surfactants, with cholesterol. DOX was loaded in NSVs using a passive and pH gradient remote loading procedure, which increased drug loading from ∼1 to ∼45%. NSVs were analyzed in terms of size, shape, size distribution, zeta potential, long-term stability, entrapment efficiency, and release kinetics, and nanocarriers having the best physiochemical parameters were selected for further in vitro tests. NSVs with and without DOX were stable and showed a sustained drug release up to 72 h. In vitro studies, with MCF-7 and MDA MB 468 cells, demonstrated that NSVs, containing Span 20, were better internalized in MCF-7 and MDA MB 468 cells than NSVs with Tween 20. NSVs increased the anticancer effect of DOX in MCF-7 and MDA MB 468 cells, and this effect is time and dose dependent. In vitro studies using metastatic and nonmetastatic breast cancer cells also demonstrated that NSVs, containing Span 20, had higher cytotoxicity than NSVs with Tween 20. The resulting data suggested that DOX-loaded NSVs could be a promising nanocarrier for the potential treatment of metastatic breast cancer.

中文翻译:


负载盐酸阿霉素的非离子表面活性剂囊泡治疗转移性和非转移性乳腺癌



盐酸阿霉素(DOX)目前用于治疗各向异性和转移性乳腺癌。由于其副作用,DOX 在癌症患者中的使用有时受到限制;为此,一些科学家尝试设计药物输送系统,以提高药物治疗效果并减少其副作用。在本研究中,我们设计、制备了非离子表面活性剂囊泡 (NSV) 并对其进行了物理化学表征,该囊泡是通过亲水性 (Tween 20) 和疏水性 (Span 20) 表面活性剂与胆固醇的不同组合自组装而获得。使用被动和 pH 梯度远程装载程序将 DOX 装载到 NSV 中,这将药物装载量从 ∼1% 增加到 ∼45%。对NSV的尺寸、形状、尺寸分布、zeta电位、长期稳定性、包封效率和释放动力学进行分析,并选择具有最佳理化参数的纳米载体进行进一步的体外测试。含有和不含 DOX 的 NSV 均稳定,并显示出长达 72 小时的持续药物释放。使用 MCF-7 和 MDA MB 468 细胞进行的体外研究表明,与含有 Tween 20 的 NSV 相比,含有 Span 20 的 NSV 在 MCF-7 和 MDA MB 468 细胞中的内化效果更好。NSV 增加了 DOX 在 MCF 中的抗癌作用。 7 和 MDA MB 468 细胞,这种作用是时间和剂量依赖性的。使用转移性和非转移性乳腺癌细胞的体外研究也表明,含有 Span 20 的 NSV 比含有 Tween 20 的 NSV 具有更高的细胞毒性。结果数据表明,负载 DOX 的 NSV 可能是一种有前景的纳米载体,可用于治疗转移性乳腺癌。
更新日期:2021-02-02
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