Efficacy of a Zn-based metalorganic framework doped with benznidazole on acute experimental Trypanosoma cruzi infection

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Abstract

Metal-Organic Frameworks (MOFs) have are known to enhance the activity of compounds when used as drug carriers due to their ability to cross the cell membrane, allowing for controlled and selective release. In this study, the effect of BNZ@Zn-MOFs on the acute phase of infection was evaluated in a mouse model. The particles were obtained by electroelution (EL), doped with BZN by mechanochemistry and characterized by scanning electron microscopy (SEM), infrared spectroscopy (FTIR) and X-ray diffraction (XRD). BNZ@Zn-MOF released 80% of the BZN after 3 h. No cytotoxicity was observed in NIH-3T3 and HeLa cells. Antiparasitic activity was observed in a model of acute experimental infection in BALB/c mice, using a dose 250 times lower than that required for free BZN. PCR analysis showed no parasite DNA in the tissues of treated mice. Hematoxylin-eosin staining revealed no apparent damage to tissue architecture. Serum levels of liver function enzymes remained unchanged. The use of suboptimal doses of BZN in this delivery system allows the maintenance of drug activity and may facilitate a significant reduction in the side effects caused by drug administration in the treatment of Chagas disease.

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