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.

Leishmaniasis, caused by protozoa of the genus Leishmania spp., is a neglected tropical disease that poses a significant challenge to the public health in tropical and subtropical regions, affecting mainly low-income individuals. Current therapies are limited due to severe adverse reactions to currently available drugs, high cost, low patient adherence, and even the emergence of resistant strains. Examining safer and more effective alternatives, natural compounds such as phytol – a diterpene derived from chlorophyll – have attracted attention due to their broad biological activities. To increase their solubility, stability, and cell delivery, nanotechnology-based systems, such as nanoemulsions (NEs), represent a promising approach. In this study, soybean oil nanoemulsions loaded with phytol (PHYT-NE) were developed using the phase inversion composition (PIC) method, and then characterized and evaluated. The PHYT-NE had a mean droplet diameter close to 200 nm, a polydispersity index of less than 0.2, spherical shape, and a pH value compatible with cutaneous application. The formulation showed high colloidal stability for at least 30 days of storage and at least 15 days even under stress conditions, with no signs of macroscopic instability or changes in droplet size. The cytocompatibility of NEs was confirmed in 3T3 fibroblasts at the concentrations tested, indicating potential safety for in vivo trials. Notably, PHYT-NE exhibited significant time-dependent leishmanicidal activity against Leishmania amazonensis promastigotes, with lower IC₅₀ values (up to five times lower at 48 hours) and up to 75% parasite death after 48 hours, showing greater antiparasitic activity compared to that of free phytol. Although the use of promastigotes represents a limitation, this model was used as a proof-of-concept, with promising evidence of the potential of PHYT-NE. Future studies in macrophage models infected with intracellular amastigotes will be essential to confirm the observed efficacy and validate the potential of PHYT-NE as a safe and effective topical therapy for cutaneous leishmaniasis.

Reported accidents involving scorpion poisoning by Tityus serrulatus are the most frequent in Brazil. The only specific treatment for envenomation is the administration of antivenoms associated with traditional adjuvants. Novel adjuvants are studied to reduce or avoid side effects and potentialize the efficacy of conventional serum. In this study, poly(lactic acid) nanoparticles were functionalized with polyethylenimine for loading peptides and proteins of T. serrulatus venom, and their use as a potential immunoadjuvant was evaluated. The protein loading efficiency of about 100% and the polyacrylamide gel electrophoresis assay confirmed the success of venom loading. Dynamic light scattering and zeta potential analysis supported small and narrow-sized cationic functionalized nanoparticles. Atomic force microscopy and scanning electron microscopy images showed nanoparticles with a spherical and smooth shape. The stability of tested formulations was accessed for six weeks, and the sustained release of proteins controlled by diffusion mechanism was also measured. Finally, in vivo immunization in BALB/c mice showed superior efficacy of the T. serrulatus venom protein-loaded nanoparticles compared to the traditional aluminum hydroxide immunoadjuvant. Thus, the formulations shown are promising nanocarriers to be used as a biotechnological approach to immunotherapy against scorpion envenomation.