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Novel nanoparticles for oral insulin delivery via the paracellular pathway

机译：通过细胞旁途径口服胰岛素的新型纳米颗粒

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摘要

Novel nanoparticles (NPs) coated with chitosan which allow insulin to be administered orally were developed. The NPs could transiently and reversibly open the tight junctions in Caco-2 cell monolayers, thus increasing their paracellular permeability. After oral administration of the FITC-labelled NPs, fluorescence signals, co-localized with ZO-1 proteins, were observed at cell-cell contact sites in the small intestine of rats. The intensity of fluorescence signals observed at the duodenum was stronger and appeared at a deeper level than at the jejunum and the ileum. The insulin-loaded NPs suspended in water were stable in typical storage conditions. Release of the loaded insulin depended greatly on the stability of the NPs at distinct pH environments. Oral administration of insulin in the form of NPs in diabetic rats demonstrated a sustained effect of decreasing the blood glucose level over at least 10 h, indicating the effect of the prepared NPs in enhancing the absorption of fully functional insulin.
机译：开发了用壳聚糖包被的新型纳米颗粒（NP），该纳米颗粒允许胰岛素口服。 NP可以瞬时和可逆地打开Caco-2细胞单层中的紧密连接，从而增加它们的细胞旁通透性。口服FITC标记的NP后，在大鼠小肠的细胞接触部位观察到与ZO-1蛋白共定位的荧光信号。与空肠和回肠相比，在十二指肠观察到的荧光信号强度更强并且显示的水平更高。悬浮在水中的装载胰岛素的NP在典型的储存条件下稳定。负载的胰岛素的释放在很大程度上取决于NP在不同pH环境下的稳定性。在糖尿病大鼠中以NPs形式口服胰岛素表现出持续降低血糖水平的效果，持续时间至少为10小时，这表明所制备的NPs可以增强全功能胰岛素的吸收。

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