de Freitas Oliveira Johny Wysllas, da Silva Mariana Farias Alves, Damasceno Igor Zumba, Rocha Hugo Alexandre Oliveira, da Silva Júnior Arnóbio Antônio, Silva Marcelo Sousa
Immunoparasitology Laboratory, Department of Clinical and Toxicological Analysis, Centre of Health Sciences, Federal University of Rio Grande do Norte, Natal 59012-570, Brazil.
Programa de Pós-Graduação em Bioquímica, Department of Biochemistry, Centro de Biociências, Universidade Federal do Rio Grande do Norte, Natal 59078-970, Brazil.
Pharmaceutics. 2022 Feb 24;14(3):497. doi: 10.3390/pharmaceutics14030497.
is a protozoan parasite responsible for Chagas disease, which affects millions around the world and is not treatable in its chronic stage. Sodium diethyldithiocarbamate is a compound belonging to the carbamate class and, in a previous study, demonstrated high efficacy against , showing itself to be a promising compound for the treatment of Chagas disease. This study investigates the encapsulation of sodium diethyldithiocarbamate by poly-lactic acid in nanoparticles, a system of biodegradable nanoparticles that is capable of reducing the toxicity caused by free DETC against cells and maintaining the antiparasitic activity. The nanosystem PLA-DETC was fabricated using nanoprecipitation, and its physical characterization was measured via DLS, SEM, and AFM, demonstrating a small size around 168 nm and a zeta potential of around -19 mv. Furthermore, the toxicity was determined by MTT reduction against three cell lines (VERO, 3T3, and RAW), and when compared to free DETC, we observed a reduction in cell mortality, demonstrating the importance of DETC nanoencapsulation. In addition, the nanoparticles were stained with FITC and put in contact with cells for 24 h, followed by confirmation of whether the nanosystem was inside the cells. Lastly, the antiparasitic activity against different strains of in trypomastigote forms was determined by resazurin reduction and ROS production, which demonstrated high efficacy towards equal to that of free DETC.
是一种导致恰加斯病的原生动物寄生虫,该病影响着全球数百万人,且在慢性阶段无法治疗。二乙基二硫代氨基甲酸钠是一种属于氨基甲酸盐类的化合物,在先前的一项研究中,它对[寄生虫名称未给出]显示出高效性,表明自身是治疗恰加斯病的一种有前景的化合物。本研究考察了聚乳酸对二乙基二硫代氨基甲酸钠的纳米粒包封情况,这是一种可生物降解的纳米粒系统,能够降低游离二乙基二硫代氨基甲酸钠对细胞造成的毒性并维持抗寄生虫活性。采用纳米沉淀法制备了纳米系统PLA - DETC,并通过动态光散射(DLS)、扫描电子显微镜(SEM)和原子力显微镜(AFM)对其进行物理表征,结果显示其粒径约为168 nm,zeta电位约为 - 19 mV。此外,通过MTT法检测了对三种细胞系(VERO、3T3和RAW)的毒性,与游离二乙基二硫代氨基甲酸钠相比,我们观察到细胞死亡率降低,证明了二乙基二硫代氨基甲酸钠纳米包封的重要性。另外,用异硫氰酸荧光素(FITC)对纳米粒进行染色,并使其与细胞接触24小时,随后确认纳米系统是否进入细胞内。最后,通过刃天青还原法和活性氧(ROS)生成法测定了对不同[寄生虫名称未给出]锥鞭毛体形式菌株的抗寄生虫活性,结果表明其对[寄生虫名称未给出]的高效性与游离二乙基二硫代氨基甲酸钠相当。