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新型纳米囊泡载体用于伏立诺他的研制:体外抗癌疗效评价。

Development of New Nanoniosome Carriers for Vorinostat: Evaluation of Anticancer Efficacy In Vitro.

机构信息

Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.

Arasto Pharmaceutical Chemicals Inc., Yousefabad, Jahanarar Avenue, Tehran, Iran.

出版信息

J Pharm Sci. 2024 Aug;113(8):2584-2594. doi: 10.1016/j.xphs.2024.05.025. Epub 2024 May 25.

Abstract

Vorinostat (VST) is a chemotherapeutic agent administrated for various types of cancers. However, it suffers from side effects and chemoresistance that reduce its application. Different nanoniosomes comprised Span 20, 60, 65 and 80 were prepared by the thin film hydration method and loaded with VST. The nanoniosomes were physicochemically characterized using particle size analysis and field emission scanning electron microscopy. The best formulation that was prepared using Span 65 (VST-NN-S65) included vesicle size of 127 nm with a narrow size distribution. VST-NN-S65 had an entrapment efficiency and loading capacity of 81.3 ± 5.1 and 32.0 ± 3.9 %, respectively. Drug release rate measurements showed that 90 % of VST was liberated within 1 h. Cytotoxicity assessments of VST-NN-S65 in HeLa and MCF7 cells indicated significant improvement in the effectiveness of VST, compared to the VST suspension. For VST-NN-S65, IC50 values of 26.3 and 6.6 μg mL were obtained for HeLa and MCF7 cell lines, respectively. In situ apoptosis detection by the TUNEL assay revealed that apoptosis mainly occurred in the cell lines.

摘要

伏立诺他(VST)是一种用于多种癌症的化疗药物。然而,它存在副作用和化疗耐药性,限制了其应用。通过薄膜水化法制备了不同的由 Span 20、60、65 和 80 组成的纳米囊泡,并将其负载 VST。通过粒径分析和场发射扫描电子显微镜对纳米囊泡进行了物理化学特性分析。使用 Span 65 制备的最佳配方(VST-NN-S65)包括囊泡大小为 127nm,具有较窄的粒径分布。VST-NN-S65 的包封效率和载药量分别为 81.3±5.1%和 32.0±3.9%。药物释放率测量表明,90%的 VST 在 1 小时内释放。VST-NN-S65 在 HeLa 和 MCF7 细胞中的细胞毒性评估表明,与 VST 混悬液相比,VST 的有效性显著提高。对于 VST-NN-S65,HeLa 和 MCF7 细胞系的 IC50 值分别为 26.3 和 6.6μg/mL。原位凋亡检测 TUNEL 试验表明,凋亡主要发生在细胞系中。

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