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.
Highlights
Chagas disease (CD) is a zoonosis caused by the flagellated parasite Trypanosoma cruzi that affects principally South America
The quantitative analysis revealed that NPD resulted in an entrapment efficiency of around 72% and a drug loading level of 3.63% that corresponds to a final drug concentration of 200 μg/mL
The Poly-lactic acid (PLA)-DETC nanosystem presents high stability and a small size of around ~164 nm, which was verified by Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and DLS analyzes
Summary
Chagas disease (CD) is a zoonosis caused by the flagellated parasite Trypanosoma cruzi that affects principally South America. Pharmaceutics 2022, 14, 497 for CD offered by the World Health Organization is benznidazole and nifurtimox. These drugs present high cytotoxicity, cause severe damage to the patients, and present low efficacy against chronic stages of CD due to their low bioavailability to reach the parasite inside the cells [3,4,5]. Sodium diethyldithiocarbamate (DETC) demonstrated high antiparasitic activity against parasites Trypanosoma cruzi and Leishmania sp., which belong to the Trypanosomatidae family. The mechanism associated with its efficacy is based on the metal chelator activity and the stimulation of reactive oxygen species (ROS), causing damage to the parasite. The mechanisms are important to eliminate the parasite; they could cause some damage to the patient, as demonstrated in in vitro experiments [6,7,8,9]
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