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壳聚糖-吡喹酮和壳聚糖-阿苯达唑纳米颗粒对细粒棘球绦虫中绦期幼虫的体外和体内作用

In vitro and in vivo effects of chitosan-praziquantel and chitosan-albendazole nanoparticles on Echinococcus granulosus Metacestodes.

作者信息

Torabi Negin, Dobakhti Faramarz, Faghihzadeh Soghrat, Haniloo Ali

机构信息

Department of Parasitology and Mycology, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Mahdavi Blvd., Shahrak Karmandan, P.O. Box 45139-56111, Zanjan, Iran.

School of Pharmacy, ZUMS, Zanjan, Iran.

出版信息

Parasitol Res. 2018 Jul;117(7):2015-2023. doi: 10.1007/s00436-018-5849-z. Epub 2018 Apr 3.

Abstract

Cystic echinococcosis (CE), which is caused by the metacestode of Echinococcus granulosus, is one of the most important zoonoses affecting humans. Benzimidazoles (in particular albendazole) and praziquantel (PZQ) are effective against CE, but poor water solubility of these agents often leads to inadequate results. Here, we evaluate the effects of chitosan-albendazole (ChABZ) and chitosan-praziquantel (ChPZQ) nanoparticles as a new formulation on hydatid cysts both in vitro and in vivo. Developed microcysts in culture were treated with different concentrations of ChABZ and ChPZQ nanoparticles (either alone or in combination), and ABZ + PZQ suspension. The viability rate of microcysts was used to evaluate the drug efficacies. In addition, the prophylactic and therapeutic effects of the drugs were studied on infected DBA/2 mice. Transmission electron microscopy was used to observe the ultra-structural changes. The viability rate of microcysts and differences in cyst weights were compared by ANOVA, and the cyst numbers were compared using the Kruskal-Wallis test. The combination of ChABZ + ChPZQ nanoparticles was more effective than the ABZ + PZQ suspension in vitro (p < 0.05). In prophylaxy, a significant reduction was observed both in size and in number of the cysts in ChABZ + ChPZQ nanoparticle groups compared with the control group (p < 0.05). In the therapeutic stage, however, this treatment only reduced the cyst numbers. Degeneration of the microcysts treated with the drugs was evident in the ultra-structural imaging. Overall, the nanoparticulate drugs were more effective than their suspension counterparts, but further studies are recommended to evaluate the full potential of these nanoparticles in the treatment of human CE.

摘要

囊型包虫病(CE)由细粒棘球绦虫的中绦期幼虫引起,是影响人类的最重要的人畜共患病之一。苯并咪唑类药物(特别是阿苯达唑)和吡喹酮(PZQ)对CE有效,但这些药物的水溶性差常常导致治疗效果不佳。在此,我们评估壳聚糖 - 阿苯达唑(ChABZ)和壳聚糖 - 吡喹酮(ChPZQ)纳米颗粒作为一种新制剂在体外和体内对包虫囊肿的作用。用不同浓度的ChABZ和ChPZQ纳米颗粒(单独或联合使用)以及阿苯达唑+吡喹酮混悬液处理培养中形成的微囊肿。微囊肿的存活率用于评估药物疗效。此外,还研究了这些药物对感染的DBA/2小鼠的预防和治疗作用。使用透射电子显微镜观察超微结构变化。通过方差分析比较微囊肿的存活率和囊肿重量差异,使用Kruskal-Wallis检验比较囊肿数量。在体外,ChABZ + ChPZQ纳米颗粒组合比阿苯达唑+吡喹酮混悬液更有效(p <0.05)。在预防方面,与对照组相比,ChABZ + ChPZQ纳米颗粒组的囊肿大小和数量均显著减少(p <0.05)。然而,在治疗阶段,这种治疗仅减少了囊肿数量。在超微结构成像中,用药物处理的微囊肿退变明显。总体而言,纳米颗粒药物比其混悬液对应物更有效,但建议进一步研究以评估这些纳米颗粒在治疗人类CE中的全部潜力。

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