Document details

In Vitro Validation of Antiparasitic Activity of PLA-Nanoparticles of Sodium Diethyldithiocarbamate against Trypanosoma cruzi

Author(s): 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

Date: 2022

Persistent ID: http://hdl.handle.net/10362/147867

Origin: Repositório Institucional da UNL

Subject(s): Chagas disease; Nanoparticle; Nanoprecipitation; Sodium diethyldithiocarbamate; Trypanosoma cruzi; QR Microbiology; QD Chemistry; Pharmaceutical Science; Parasitology; Drug Discovery; Infectious Diseases; Medical Laboratory Technology; Molecular Biology; SDG 3 - Good Health and Well-being; SDG 9 - Industry, Innovation, and Infrastructure


Description

Funding Information: This research was funded by Global Health and Tropical Medicine: Grant number IHMT-UID/multi/04413/2013 and Grant number PTDC/CVT-CVT/28908/2017, FCT-Portugal.We would like to thank João Aristeu da Rosa and Aline Rimodi Rimeiro at UNESP (Universidade Estadual de São Paulo) Araraquara (Brazil) for offering four different strains of T. cruzi. JWFO and MFAS give thanks to their financial support (PhD and post-doctoral fellowships) provided by Capes/Brazil; MSS, AASJ, and HAOR give thanks to CNPq/Brazil for the Research Grant (Bolsa de Produtividade). We would also like to thank the Department of Materials Engineering at UFRN for affording us the use of their scanning electron microscope, and the Department of Biochemistry at UFRN for affording us the use of their culture room. We thank Laysa Ohana for reviewing and editing the English version of the manuscript. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

Trypanosoma cruzi 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 T. cruzi, 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 T. cruzi in trypomastigote forms was determined by resazurin reduction and ROS production, which demonstrated high efficacy towards T. cruzi equal to that of free DETC.

Document Type Journal article
Language English
Contributor(s) Instituto de Higiene e Medicina Tropical (IHMT); Global Health and Tropical Medicine (GHTM); Vector borne diseases and pathogens (VBD); RUN
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