TY - JOUR
T1 - In Vitro Validation of Antiparasitic Activity of PLA-Nanoparticles of Sodium Diethyldithiocarbamate against Trypanosoma cruzi
AU - de Freitas Oliveira, Johny Wysllas
AU - da Silva, Mariana Farias Alves
AU - Damasceno, Igor Zumba
AU - Rocha, Hugo Alexandre Oliveira
AU - da Silva Júnior, Arnóbio Antônio
AU - Silva, Marcelo Sousa
N1 - 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.
PY - 2022/3
Y1 - 2022/3
N2 - 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.
AB - 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.
KW - Chagas disease
KW - Nanoparticle
KW - Nanoprecipitation
KW - Sodium diethyldithiocarbamate
KW - Trypanosoma cruzi
UR - http://www.scopus.com/inward/record.url?scp=85125676347&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14030497
DO - 10.3390/pharmaceutics14030497
M3 - Article
C2 - 35335875
AN - SCOPUS:85125676347
SN - 1999-4923
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
IS - 3
M1 - 497
ER -