Silica is frequently used in oral drug delivery; however, its biosafety, particularly concerned with its nanostructure, has not been comprehensively studied yet. Here, the in vitro and in vivo biosafety of two types of silica (A200, nano-sized or micron-sized agglomerates; S350, micro-sized particles with nanopores) were compared and the possible reasons for the differences were explored. The results indicated that both A200 and S350 could inhibit the growth of Caco-2 cells by inducing apoptosis and changing the cell cycle progression. A200 showed a stronger influence than S350 in most of the in vitro experiments. In the in vivo study in KM mice, both A200 and S350 could change the blood constituents under the tested conditions; A200 also increased the levels of inflammatory factors in plasma and the numbers of CD4+ lymphocyte subsets. No obvious organic damage was observed in either the A200-treated or S350-treated groups. The transport study showed that neither A200 nor S350 were readily transported across the intestinal epithelial barrier in vitro and in vivo, but A200 could transport across the lymphatic-associated epithelium and accumulate in the Peyer's Patches, which might explain the A200-induced immune response. The increased transport of A200 might relate to its particle size, dispersion state and specific surface area. In conclusion, these results demonstrated that A200 and S350 exhibited diverse biosafety aspects, which correlated with their different nanostructures. We believe this study will provide some scientific information about the biosafety of A200 and S350 for their applications in oral drug delivery systems.

中文翻译：

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两种不同纳米结构二氧化硅的生物安全性研究及机理比较。


二氧化硅经常用于口服药物输送；然而，其生物安全性，特别是其纳米结构的生物安全性尚未得到全面研究。在这里，比较了两种类型二氧化硅（A200，纳米尺寸或微米尺寸的团聚体；S350，具有纳米孔的微米尺寸颗粒）的体外和体内生物安全性，并探讨了差异的可能原因。结果表明，A200和S350均可通过诱导细胞凋亡和改变细胞周期进程来抑制Caco-2细胞的生长。在大多数体外实验中，A200 表现出比 S350 更强的影响。在KM小鼠体内研究中，A200和S350在测试条件下均能改变血液成分； A200 还增加了血浆中炎症因子的水平和 CD4+ 淋巴细胞亚群的数量。 A200 处理组和 S350 处理组均未观察到明显的器质性损伤。转运研究表明，在体外和体内，A200 和 S350 都不容易转运穿过肠上皮屏障，但 A200 可以转运穿过淋巴相关上皮并在派尔氏淋巴结中积聚，这可能解释了 A200 诱导的免疫反应。 A200 的传输增加可能与其粒径、分散状态和比表面积有关。总之，这些结果表明 A200 和 S350 表现出不同的生物安全性，这与其不同的纳米结构相关。我们相信这项研究将为 A200 和 S350 在口服给药系统中的应用提供一些有关其生物安全性的科学信息。