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基于脲基修饰壳聚糖衍生物的阿莫西林-UCCs-2/TPP 纳米粒的抗幽门螺杆菌效果和靶向递药性能。

Anti-Helicobacterpylori effectiveness and targeted delivery performance of amoxicillin-UCCs-2/TPP nanoparticles based on ureido-modified chitosan derivative.

机构信息

Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China; The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China.

Department of Pharmaceutics, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Int J Biol Macromol. 2018 Aug;115:367-374. doi: 10.1016/j.ijbiomac.2018.04.070. Epub 2018 Apr 14.

DOI:10.1016/j.ijbiomac.2018.04.070
PMID:29660462
Abstract

The amoxicillin-UCCs-2/TPP nanoparticles constructed with ureido-modified chitosan derivative UCCs-2 and sodium tripolyphosphate (TPP) played an important role to deliver drug to achieve more efficacious and specific eradication of Helicobacterpylori (H. pylori) in vitro. In this study, the anti-H. pylori effectiveness in vivo and uptake mechanism was investigated in details, including the effect of temperature, pH values and the addition of competitive substrate urea on uptake. Compared with unmodified nanoparticles, a more efficacious and specific anti-H. pylori activities were obtained in vivo by using this biological chitosan derivative UCCs-2. Histological staining and immunological analysis verified that the amoxicillin-UCCs-2/TPP nanoparticles could diminish the proinflammatory cytokines levels and alleviate the inflammatory damages caused by H. pylori infection. The uredio-modified nanoparticles also have favorable gastric retention property, which is beneficial for the oral drug delivery to targeted eradicate H. pylori infection in stomach. These findings suggest that this targeted drug delivery system may serve for specific treatment of H. pylori infection both in vitro and in vivo, which can also be used as promising nanocarriers for other therapeutic reagents to target H. pylori.

摘要

采用脲基修饰壳聚糖衍生物 UCCs-2 和三聚磷酸钠(TPP)构建的阿莫西林-UCCs-2/TPP 纳米粒在将药物递送至体外实现更有效和更特异的幽门螺杆菌(H. pylori)根除方面发挥了重要作用。在这项研究中,详细研究了体内抗 H. pylori 的效果和摄取机制,包括温度、pH 值以及添加竞争性底物尿素对摄取的影响。与未修饰的纳米粒相比,通过使用这种生物壳聚糖衍生物 UCCs-2,在体内获得了更有效和更特异的抗 H. pylori 活性。组织学染色和免疫分析证实,阿莫西林-UCCs-2/TPP 纳米粒可以降低促炎细胞因子的水平并减轻 H. pylori 感染引起的炎症损伤。脲基修饰的纳米粒还具有良好的胃滞留特性,有利于口服药物递送至胃部以靶向根除 H. pylori 感染。这些发现表明,这种靶向药物递送系统可能在体外和体内都可用于 H. pylori 感染的特异性治疗,也可作为有前途的纳米载体用于其他针对 H. pylori 的治疗试剂。

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