Trypanosoma cruzi: Does the intake of nanoencapsulated benznidazole control acute infections?

Chagas Disease (CD) affects around eight million people worldwide. It is considered a neglected disease that presents few treatment options with efficacy only in the acute phase. Nanoparticles have many positive qualities for treating parasite infections and may be effectively and widely employed in...

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Published in:	Experimental parasitology Vol. 249; p. 108520
Main Authors:	Dutra da Silva, Aniélen, Fracasso, Mateus, Bottari, Nathieli B., Gundel, Samanta, Ourique, Aline F., Assmann, Charles E., Ferreira, Danielle A.S.P., Castro, Milagros F.V., Reichert, Karine P., de Souza, Lucas A.F., da Veiga, Marcelo L., da Rocha, Maria Izabel U.M., Monteiro, Silvia G., Morsch, Vera M., Chitolina Schetinger, Maria Rosa, da Silva, Aleksandro S.
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 01-06-2023
Subjects:	Acute phase Animals Chagas disease Chagas Disease - parasitology Female Mice Nanocapsules Nitroimidazoles - pharmacology Nitroimidazoles - therapeutic use Parasitemia - drug therapy Parasitemia - parasitology Pathogenesis Treatment Trypanocidal Agents - pharmacology Trypanocidal Agents - therapeutic use Trypanosoma cruzi Chagas disease Treatment Pathogenesis Acute phase Nanocapsules
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Summary:	Chagas Disease (CD) affects around eight million people worldwide. It is considered a neglected disease that presents few treatment options with efficacy only in the acute phase. Nanoparticles have many positive qualities for treating parasite infections and may be effectively and widely employed in clinical medicine. This research aimed to evaluate the nanoencapsulated benznidazole treatment in animals experimentally infected with Trypanosoma cruzi. To analyze the treatment efficacy, we evaluated survival during thirty days, parasitemia, genotoxicity, and heart and liver histopathology. Thirty-five female Swiss mice were organized into seven groups characterizing a dose curve: A – Negative control (uninfected animals), B – Positive control (infected animals), C – Benznidazole (BNZ) 100 mg/kg (infected animals), D – 5 mg/kg Benznidazole nanocapsules (NBNZ) (infected animals), E − 10 mg/kg Benznidazole nanocapsules (infected animals), F – 15 mg/kg Benznidazole nanocapsules (infected animals), G – 20 mg/kg Benznidazole nanocapsules (infected animals). The animals were infected with the Y strain of T. cruzi intraperitoneally. The treatment was administered for eight days by oral gavage. It was possible to observe that the treatment with the highest NBNZ dose presented efficacy similar to the standard benznidazole drug. The 20 mg/kg NBNZ dose was able to reduce parasitemia, increase survival, and drastically reduce heart and liver tissue damage compared to the 100 mg/kg BNZ dose. Moreover, it showed a lower DNA damage index than the BNZ treatment. In conclusion, the nanoencapsulation of BNZ promotes an improvement in parasite proliferation control with a five times smaller dose relative to the standard dose of free BNZ, thus demonstrating to be a potential innovative therapy for CD. [Display omitted] •Benznidazole is a cytotoxic compound to cell DNA.•Nanoencapsulated benznidazole improve treatment with lower dose and reduced cytotoxicity.•Chagas disease promotes tissue damage in several organs.•Benznidazole may increase the survival in T. cruzi infection.•Nanoencapsulated benznidazole protect cardiac tissue invasion in T. cruzi infection.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0014-4894 1090-2449
DOI:	10.1016/j.exppara.2023.108520