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米替福新-银纳米颗粒杂化复合物的合成与评价:与苯硝唑对克氏锥虫的协同相互作用

Synthesis and Evaluation of a Hybrid Miltefosine-Silver Nanoparticle Complex: Synergistic Interaction with Benznidazole Against Trypanosoma cruzi.

作者信息

Özel Yener, Çavuş İbrahim, Tokay Feyzullah, Bağdat Sema, Özbilgin Ahmet

机构信息

Department of Medical Microbiology, Balıkesir University Medical Faculty, Balikesir, Türkiye.

Department of Medical Parasitology, Manisa Celal Bayar University Medical Faculty, Manisa, Türkiye.

出版信息

Acta Parasitol. 2025 Jun 12;70(3):135. doi: 10.1007/s11686-025-01074-3.

DOI:10.1007/s11686-025-01074-3
PMID:40504446
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12162769/
Abstract

OBJECTIVE

Chagas disease is an infectious disease classified under neglected tropical diseases and caused by the protozoan parasite Trypanosoma cruzi. This study aimed to investigate the cytotoxic activity, antitrypanosomal efficacy, and combination effects with benznidazole of hybrid silver nanoparticles (AgNPs) synthesized with miltefosine against T. cruzi epimastigotes.

METHODS

In this study, a hybrid miltefosine (Mil)-silver nanoparticle (OA-MilAg-NP) complex was synthesized. The nanoparticles were characterized using FT-IR spectroscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM) analyses. The cytotoxicity of the nanoparticles was assessed in L929 fibroblast cells, while their antitrypanosomal activity was evaluated against a Trypanosoma cruzi ATCC 50828 strain using the broth microdilution method. The interaction between the nanoparticle complex or miltefosine and benznidazole was analyzed using the checkerboard method.

RESULTS

FT-IR analysis demonstrated that the amylose surface was successfully coated with silver and miltefosine, confirming the successful synthesis of the hybrid complex. SEM analysis revealed that the nanoparticles exhibited a spherical morphology with varying sizes, while TEM analysis determined their sizes ranged between 10.14 and 18.42 nm. The OA-MilAg-NP complex exhibited high antitrypanosomal activity and a selectivity index twice as high as that of miltefosine. Synergistic interactions were observed in the combinations of the OA-MilAg-NP complex or miltefosine with benznidazole.

CONCLUSION

The development of novel bioactive compounds with lower toxicity compared to traditional drugs has become essential for the treatment of Chagas disease. Drug repurposing combined with nanotechnology applications holds significant potential for improving therapeutic outcomes. The hybridization of miltefosine with silver nanoparticles, demonstrating strong antitrypanosomal activity and synergistic effects with benznidazole, may fill critical gaps in the literature.

摘要

目的

恰加斯病是一种被归类为被忽视热带病的传染病,由原生动物寄生虫克氏锥虫引起。本研究旨在调查用米替福新合成的杂化银纳米颗粒(AgNPs)对克氏锥虫前鞭毛体的细胞毒性活性、抗锥虫功效以及与苯硝唑的联合作用。

方法

在本研究中,合成了一种杂化米替福新(Mil)-银纳米颗粒(OA-MilAg-NP)复合物。使用傅里叶变换红外光谱(FT-IR)、透射电子显微镜(TEM)和扫描电子显微镜(SEM)分析对纳米颗粒进行了表征。在L929成纤维细胞中评估了纳米颗粒的细胞毒性,同时使用肉汤微量稀释法评估了它们对克氏锥虫ATCC 50828菌株的抗锥虫活性。使用棋盘法分析了纳米颗粒复合物或米替福新与苯硝唑之间的相互作用。

结果

FT-IR分析表明直链淀粉表面成功包覆了银和米替福新,证实了杂化复合物的成功合成。SEM分析显示纳米颗粒呈现出大小各异的球形形态,而TEM分析确定其大小在10.14至18.42纳米之间。OA-MilAg-NP复合物表现出高抗锥虫活性,其选择性指数是米替福新的两倍。在OA-MilAg-NP复合物或米替福新与苯硝唑的组合中观察到协同相互作用。

结论

开发与传统药物相比毒性更低的新型生物活性化合物对于恰加斯病的治疗已变得至关重要。药物再利用与纳米技术应用相结合在改善治疗效果方面具有巨大潜力。米替福新与银纳米颗粒的杂化显示出强大的抗锥虫活性以及与苯硝唑的协同作用,可能填补文献中的关键空白。

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