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

Abstract

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.

Use of Nanocarriers Containing Antitrypanosomal Drugs for the Treatment of Chagas Disease

“…The article that obtained the lowest score was [ 3 ], as it only conducted in vitro assays, obtaining a null score in all the topics related to in vivo assays, in addition to not presenting other issues such as physicochemical characterization and the nanometric size of the nanocarrier. The articles [ 2 , 3 , 5 , 22 , 23 , 24 ] received a zero for the topics of ethics statement, study design, animals, sample size, and in vivo studies, as they did not present in vivo studies, only in vitro ones.…”

The repositioned drugs disulfiram/diethyldithiocarbamate combined to benznidazole: Searching for Chagas disease selective therapy, preventing toxicity and drug resistance

“…Both DETC and DSF express antiparasitic activities upon T. cruzi (Lane et al, 1996;de Freitas Oliveira et al, 2021;de Freitas Oliveira et al, 2022) and Leishmania (Khouri et al, 2010;Celes et al, 2016;Mazur et al, 2019). In macrophage cultures, DETC caused destruction of intracellular amastigotes with little effect on macrophage spreading pattern.…”

Alternative Approaches for the Treatment of Chagas Disease

“…In 2022, Rolon et al developed solid nanomedicines using SNEDDS, and Oliveira et al in 2022, investigated PLA-nanoparticles for the encapsulation of sodium diethyldithiocarbamate (DETC), both demonstrating effective drug release, reduced toxicity, and potent antiparasitic effect against different T. cruzi strains. [174][175] Ferraz et al (2021 and 2020) utilized ZIF-8 and BNZ as carriers to develop medication delivery devices sensitive to changes in pH, respectively, showing controlled and prolonged release of BNZ under varying pH conditions. [176][177] In 2020, Silva et al developed PLGA nanoparticles as a delivery system for the gold complex, demonstrating controlled release behavior by utilizing the diffusion and relaxation properties of the polymeric matrix, with high encapsulation efficiency and stability over time.…”

“…developed solid nanomedicines using SNEDDS, and Oliveira et al. in 2022 , investigated PLA‐nanoparticles for the encapsulation of sodium diethyldithiocarbamate (DETC), both demonstrating effective drug release, reduced toxicity, and potent antiparasitic effect against different T. cruzi strains [174–175] . Ferraz et al .…”