Benznidazole-Loaded Polymeric Nanoparticles for Oral Chemotherapeutic Treatment of Chagas Disease.

Chagas disease (CD) is a worldwide public health problem. Benznidazole (BZ) is the drug used to treat it. However, in its commercial formulation, it has significant side effects and is less effective in the chronic phase of the infection. The development of particulate systems containing BZ is therefore being promoted. The objective of this investigation was to develop polymeric nanoparticles loaded with BZ and examine their trypanocidal impact in vitro. Two formulas (BNP1 and BNP2) were produced through double emulsification and freeze drying. Subsequent to physicochemical and morphological assessment, both formulations exhibited adequate yield, average particle diameter, and zeta potential for oral administration. Cell viability was assessed in H9C2 and RAW 264.7 cells in vitro, revealing no cytotoxicity in cardiomyocytes or detrimental effects in macrophages at specific concentrations. BNP1 and BNP2 enhanced the effect of BZ within 48 h using a treatment of 3.90 µg/mL. The formulations notably improved NO reduction, particularly BNP2. The findings imply that the compositions are suitable for preclinical research, underscoring their potential as substitutes for treating CD. This study aids the quest for new BZ formulations, which are essential in light of the disregard for the treatment of CD and the unfavorable effects associated with its commercial product.

Different infective forms trigger distinct lesions in the colon during experimental Chagas disease.

With the control of vectorial transmission of Chagas disease caused by metacyclic trypomastigotes (MT) in endemic countries, other pathways of infection have become important. The infection caused by blood trypomastigotes (BT) is relevant in places where the blood transfusion and organ transplantation are poorly controlled. This study aimed to evaluate immunopathogenic parameters in the colon during the acute and chronic phases of experimental infection in Swiss mice infected with BT or MT forms of VL-10 strain of Trypanosoma cruzi. We have found that animals infected with MT forms presented lower survival rate, and higher tissue parasitism in the acute phase of the disease, which may be associated with the exacerbated activation of the immune system with the production of pro-inflammatory cytokines even in the chronic phase of infection. Taken together, these results can also be associated to the maintenance of the inflammatory process in chronic phase and an earlier denervation of myenteric plexus in colon. These findings emphasized the importance of the inoculum source and the strain, once different forms of different strains seem to promote distinct diseases.