Selective Antiprotozoal Activity of Nitric Oxide-releasing Chitosan Nanoparticles Against Trypanosoma cruzi: Toxicity and Mechanisms of Action

Author(s): Cesar Armando Contreras Lancheros, Milena Trevisan Pelegrino, Danielle Kian, Eliandro Reis Tavares, Priscila Mazzochi Hiraiwa, Samuel Goldenberg, Celso Vataru Nakamura, Lucy Megumi Yamauchi, Phileno Pinge-Filho, Amedea Barozzi Seabra*, Sueli Fumie Yamada-Ogatta*.

Journal Name: Current Pharmaceutical Design

Volume 24 , Issue 7 , 2018

Abstract:

Background: Chagas' disease, caused by Trypanosoma cruzi, was described for the first time over a hundred years ago. Nonetheless, clinically available drugs still lack effective and selective properties. Nitric oxide (NO) produced by activated macrophages controls the progression of disease by killing the parasite.

Methods and Results: Here, chitosan nanoparticles (CS NPs) were synthesized and mercaptosuccinic acid (MSA), the NO donor precursor, was encapsulated into CS NPs, forming MSA-CS NPs, which had hydrodynamic size of 101.0±2.535 nm. Encapsulated MSA was nitrosated forming NO donor S-nitrosomercaptosuccinic acid-containing nanoparticles (S-nitroso-MSA-CS NPs). Kinetic data revealed a sustained release of NO from the nanoparticles. S-nitroso-MSA-CS NPs inhibited epimastigote proliferation and trypomastigote viability of T. cruzi, with IC50=75.0±6.5 µg·mL-1 and EC50=25.0±5.0 µg·mL-1, respectively. Treatment of peritoneal macrophages with nanoparticles decreased the number of T. cruzi-infected cells and the average number of intracellular replicative amastigotes per infected cells. Besides, the results have showed a selective behaviour of S-nitroso-MSA-CS NPs to parasites. Morphological and biochemical changes induced by these NO-releasing nanoparticles, such as cell shrinkage, cell cycle arrest, mitochondrial membrane depolarization and phosphatidylserine exposure on cell surface indicate that epimastigotes death is associated to the apoptotic pathway.

Conclusion: S-nitroso-MSA-CS NPs are promising nanocarriers for the treatment of Chagas's disease.

Keywords: Antiprotozoal activity, chitosan nanoparticles, nitric oxide nanocarrier, S-nitroso mercaptosuccinic acid, cell death, Chagas' disease.

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Article Details

VOLUME: 24
ISSUE: 7
Year: 2018
Page: [830 - 839]
Pages: 10
DOI: 10.2174/1381612824666180209105625
Price: $58

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