To develop a suitable formulation with high entrapment efficiency, etoposide-loaded poly(lactide-co-glycolide) nanoparticles (NPs) were formulated by single emulsion-solvent evaporation method by changing different formulation parameters such as drug loading, choice of organic solvent and percentage of emulsifier polyvinyl alcohol. The NPs showed higher entrapment efficiency, ~86% (with 15% (w/w) drug loading). The physicochemical parameters revealed smooth topology with size range (240–320 nm), a negative zeta potential (~19 mV) and in vitro sustained-release activity (~60% drug release in 40 days). Greater anti-proliferative activity ~100 times was observed with NPs (IC50 = 0.002 μg/ml) than that of native etoposide (IC50 = 0.2 μg/ml) in retinoblastoma cell line (Y-79). These NPs demonstrated greater (G1/S) blocking and decreased mitochondrial membrane potential as measured by flow cytometry. There was upregulation of apoptotic gene activity in NPs than native etoposide, as revealed through microarray analysis. However, this is the first ever report demonstrating the intricate modulation of genetic network affected by NPs. Collectively, these results suggest that etoposide-loaded NPs could be potentially useful as a novel drug delivery system for retinoblastoma in the future.

中文翻译：

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依托泊苷纳米颗粒的毒理基因组学：对视网膜母细胞瘤治疗中纳米技术的潜在影响。

为了开发一种具有高包封率的合适制剂，通过改变乳剂-溶剂-溶剂蒸发法改变了不同的制剂参数，如载药量，有机溶剂的选择和百分含量，来制备负载依托泊苷的聚（丙交酯-共-乙交酯）纳米颗粒（NPs）。乳化剂聚乙烯醇。NPs表现出更高的包封效率，约86％（载药量为15％（w / w））。理化参数显示其分子大小范围（240-320 nm）平滑的拓扑，ζ负电势（〜19 mV）和体外持续释放活性（40天内约60％的药物释放）。在视网膜母细胞瘤细胞系（Y-79）中，NPs（IC50 = 0.002μg/ ml）观察到的抗增殖活性比天然依托泊苷（IC50 = 0.2μg/ ml）高约100倍。通过流式细胞仪测量，这些NPs表现出更大的（G1 / S）阻滞作用和降低的线粒体膜电位。通过微阵列分析发现，NPs中的凋亡基因活性比天然依托泊苷上调。然而，这是有史以来第一份证明受NP影响的遗传网络复杂调控的报告。总的来说，这些结果表明，负载依托泊苷的NPs将来可能作为视网膜母细胞瘤的新型药物递送系统有用。如通过微阵列分析所揭示的。但是，这是有史以来第一份证明受NP影响的复杂遗传网络调控的报告。总的来说，这些结果表明，负载依托泊苷的NPs将来可能作为视网膜母细胞瘤的新型药物递送系统有用。如通过微阵列分析所揭示的。然而，这是有史以来第一份证明受NP影响的遗传网络复杂调控的报告。总的来说，这些结果表明，负载依托泊苷的NPs将来可能作为视网膜母细胞瘤的新型药物递送系统有用。