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壳聚糖包覆的中空二氧化锡纳米粒子的制备及其在提高非布索坦口服生物利用度中的应用。

Preparation of chitosan-coated hollow tin dioxide nanoparticles and their application in improving the oral bioavailability of febuxostat.

作者信息

Sun Junpeng, Du Jiaqun, Liu Xiaobang, An Jinyu, Li Yingqiao, Yu Yanan, Li Minghui, Zheng Li, Wu Chao, Hu Lili

机构信息

Pharmacy School, Jinzhou Medical University, Jinzhou, Liaoning 121001, China.

Medical College of Jinzhou Medical University, Jinzhou Medical University, 121010, China.

出版信息

Int J Pharm X. 2023 Jul 13;6:100199. doi: 10.1016/j.ijpx.2023.100199. eCollection 2023 Dec 15.

Abstract

The aim of this study was to design a chitosan-coated hollow tin dioxide nanosphere (CS-HSn) for loading febuxostat (FEB) using an adsorption method to obtain a sustained-release system (CS-HSn-FEB) to improve the oral bioavailability of FEB. The morphological characteristics of hollow tin dioxide nanospheres (HSn) and CS-HSn were analyzed by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The hemolysis test and CCK-8 test were used to assess the biosafety of HSn and CS-HSn. Powder X-ray diffraction (PXRD) and differential scanning thermal analysis (DSC) were performed on CS-HSn-FEB to analyze the drug presence status. The dissolution behavior and changes in plasma drug concentration of CS-HSn-FEB were evaluated in vitro and in vivo. Sections of intestinal tissues from SD rats were obtained to observe whether chitosan could increase the distribution of nanoparticles in the intestinal tissues. The results showed that FEB was present in CS-HSn in an amorphous state. Moreover, CS-HSn, with good biosafety, significantly improved the water solubility and oral absorption of FEB, indicating that CS-HSn has great potential to improve the intestinal absorption and oral bioavailability of insoluble drugs.

摘要

本研究的目的是设计一种壳聚糖包被的中空二氧化锡纳米球(CS-HSn),采用吸附法负载非布司他(FEB),以获得一种缓释系统(CS-HSn-FEB),从而提高FEB的口服生物利用度。通过透射电子显微镜(TEM)和动态光散射(DLS)分析中空二氧化锡纳米球(HSn)和CS-HSn的形态特征。采用溶血试验和CCK-8试验评估HSn和CS-HSn的生物安全性。对CS-HSn-FEB进行粉末X射线衍射(PXRD)和差示扫描量热分析(DSC),以分析药物的存在状态。在体外和体内评估CS-HSn-FEB的溶出行为和血浆药物浓度变化。获取SD大鼠的肠组织切片,观察壳聚糖是否能增加纳米颗粒在肠组织中的分布。结果表明,FEB以无定形状态存在于CS-HSn中。此外,具有良好生物安全性的CS-HSn显著提高了FEB的水溶性和口服吸收,表明CS-HSn在改善难溶性药物的肠道吸收和口服生物利用度方面具有巨大潜力。

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