It is hypothesized that etoposide/VP-16 nanomicellar formulation (VP-16 NMF) utilizing D-α-Tocopherol polyethylene glycol 1000 succinate (TPGS) can improve etoposide solubility and anticancer activity. The following four different concentrations of TPGS: 3, 6, 8, and 10 wt% were used to solubilize the drug. Among these four formulations, 10 wt% of TPGS loaded with VP-16 NMF dramatically enhanced etoposide apparent solubility by 26-folds compared with the native drug. The physicochemical properties of the optimized formulation were further analyzed by dynamic light scattering, X-ray powder diffraction, scanning electron microscopy, proton nuclear magnetic resonance (¹HNMR) and Fourier transform infrared spectroscopy. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) was used to assess solubility and intracellular uptake of the drug from the NMF. Cell viability assay ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H tetrazolium solution [MTS]) was performed on MCF-7 and MCF-10A cell lines to assess intracellular uptake and anticancer activity of etoposide. The MTS assay results showed that the VP-16 NMF platform provides a higher anticancer activity than the native VP-16 on the MCF-7 cells line as it integrates a dual anticancer activity of VP-16 and TPGS. LC-MS/MS data showed a threefold increase in cellular uptake of VP-16 NMF in MCF-7 cell line compared with the native etoposide. These data suggest that an optimal TPGS concentration can improve VP-16 bioavailability and efficacy with potential benefits for chemotherapy.

中文翻译：

---

自组装纳米胶束增强依托泊苷的溶解度和抗癌活性

据推测，利用 D-α-生育酚聚乙二醇 1000 琥珀酸酯 (TPGS) 的依托泊苷/VP-16 纳米胶束制剂 (VP-16 NMF) 可以提高依托泊苷的溶解度和抗癌活性。以下四种不同浓度的 TPGS：3、6、8 和 10 wt% 用于溶解药物。在这四种制剂中，与天然药物相比，负载 VP-16 NMF 的 10 wt% 的 TPGS 显着提高了依托泊苷的表观溶解度 26 倍。通过动态光散射、X射线粉末衍射、扫描电镜、质子核磁共振（¹HNMR) 和傅里叶变换红外光谱。液相色谱串联质谱 (LC-MS/MS) 用于评估药物从 NMF 的溶解度和细胞内摄取。在 MCF-7 和 MCF 上进行细胞活力测定 ([3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H 四唑溶液 [MTS]) -10A 细胞系，用于评估依托泊苷的细胞内摄取和抗癌活性。MTS 测定结果表明，VP-16 NMF 平台在 MCF-7 细胞系上提供了比天然 VP-16 更高的抗癌活性，因为它整合了 VP-16 和 TPGS 的双重抗癌活性。LC-MS/MS 数据显示，与天然依托泊苷相比，MCF-7 细胞系中 VP-16 NMF 的细胞摄取增加了三倍。