First Century of Chagas' Disease: An Overview on Novel Approaches to Nifurtimox and Benznidazole Delivery Systems

Salomón, Claudio J.

doi:10.1002/jps.23010

Cited by 68 publications

(54 citation statements)

References 42 publications

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“…Even though nanotechnology is widely applied to develop nanomedicines for several pathologies, including cancer, cardiovascular and neurodegenerative disorders, little is known about nanoformulations for the treatment of Chagas disease. 6,7 Thus, the aim of this study was to evaluate the effectiveness of BNZ nanoparticles (BNZ-nps) on trypomastigotes forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells as compared with raw BNZ (R-BNZ). Its effectiveness was also evaluated on acute T. cruzi Nicaragua (TcN) mice infection.…”

Section: Introductionmentioning

confidence: 99%

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Scalise

Arrúa

Rial

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. The aim of this study was to evaluate the effectiveness of benznidazole nanoparticles (BNZ-nps) on trypomastigote forms and on intracellular infection in mammalian cells and primary cardiac myocyte cells. Its effectiveness was also evaluated on acute Trypanosoma cruzi Nicaragua mice infection. Trypomastigotes from culture were treated with different concentrations of BNZ-nps to determine the drug concentration that lyses 50% of trypomastigotes (LC 50 ). Infected mammalian cells were incubated with different concentrations of BNZ-nps to determine the percentage of amastigote inhibition. C 3 H/HeN mice with lethal acute infection were treated with 10, 25, and 50 mg/kg/day of BNZnps for 30 and 15 days to control the survival rate of animals. BNZ-nps having a mean particle size of 63.3 nm, a size distribution of 3.35, and a zeta potential of −18.30 were successfully prepared using poloxamer 188 as a stabilizer. BNZ-nps 25 and 50 μg/mL showed no significant differences in the percentage of inhibition of infected mammalian cells. Infected mice treated with BNZ-nps (50, 25, and 10 mg/kg/day) for 30 days and with BNZ-nps (50 and 25 mg/kg/day) for 15 days presented a 100% survival, whereas the animals treated with 10 mg/kg/day for 15 days of BNZ-nps showed a 70% survival rate. The results obtained demonstrate, for the first time, that benznidazole nanoparticles are a useful and attractive approach to treat Chagas disease in infected mice.

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Section: Introductionmentioning

confidence: 99%

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Scalise

Arrúa

Rial

et al. 2016

The American Society of Tropical Medicine and Hygiene

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“…Nevertheless, although large amounts of BNZ can reach the heart and colon, as represented by the AUC 0 -6 ratios in relation to plasma, the maximum concentration in plasma may be insufficient for complete parasite elimination in organs during the chronic phase of T. cruzi infection. Recently, the improvement of Chagas disease chemotherapy has been experimentally evaluated with new formulations of BNZ, such as extended-release tablets, solid dispersions, microparticles, and nanoparticles, to increase the maintenance of the drug concentration in vivo (38)(39)(40).…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

Perin

Silva

Fonseca

et al. 2017

Antimicrob Agents Chemother

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Specific chemotherapy using benznidazole (BNZ) for Chagas disease during the chronic stage is controversial due to its limited efficacy and toxic effects. Although BNZ has been used to treat Chagas disease since the 1970s, few studies about the biodistribution of this drug exist. In this study, BNZ tissue biodistribution in a murine model and its pharmacokinetic profile in plasma were monitored. A bioanalytical high-performance liquid chromatography method with a UV detector (HPLC-UV) was developed and validated according to the European Medicines Agency for quantification of BNZ in organs and plasma samples prepared by liquidliquid extraction using ethyl acetate. The developed method was linear in the BNZ concentration, which ranged from 0.1 to 100.0 g/ml for plasma, spleen, brain, colon, heart, lung, and kidney and from 0.2 to 100.0 g/ml for liver. Validation assays demonstrated good stability for BNZ under all conditions evaluated. Pharmacokinetic parameters confirmed rapid, but low, absorption of BNZ after oral administration. Biodistribution assays demonstrated different maximum concentrations in organs and similar times to maximum concentration and mean residence times, with means of 40 min and 2.5 h, respectively. Therefore, the biodistribution of BNZ is extensive, reaching organs such as the heart and colon, which are the most relevant organs affected by Trypanosoma cruzi infection, and also the spleen, brain, liver, lungs, and kidneys. Simultaneous analyses of tissues and plasma indicated high BNZ metabolism in the liver. Our results suggest that low bioavailability, instead of inadequate biodistribution, could be responsible for therapeutic failure during the chronic phase of Chagas disease.

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“…Although the vectorial and transfusional transmission cases have been progressively reduced, Chagas' disease is still a major public health problem and one of the leading causes of morbidity, disability and mortality in Latin America. It is estimated that nearly 90 million people are at risk of infection and more than 8 million are infected, with an annual death toll of about 50,000 people in 18 endemic countries [220]. The yearly incidence rate due to vectorial transmission is estimated to be around 42,000, whereas that of congenital cases is estimated to be nearly 15,000 [221].…”

Section: Chagas' Diseasementioning

confidence: 99%

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

Zucca¹,

Scutera²,

Savoia³

2013

Current Medicinal Chemistry

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Due to the persistent lack of suitable vaccines, chemotherapy remains the only option for the treatment of patients infected by protozoan parasites. However, most available antiparasitic drugs have serious disadvantages, ranging from high cost and poor compliance to high toxicity and rapid induction of resistance. In recent decades basic research laboratories identified a considerable number of promising new molecules, but their development has not been pursued in depth by pharmaceutical firms because of poor prospects of economic return. The establishment of adequately funded public-private partnerships is currently reversing the trend. This review deals with new drugs against Plasmodium, Leishmania and Trypanosoma parasites, focusing on the molecules that are in the most advanced stage of development. The purpose of this article is to provide the reader with a panoramic view of the updated literature on the challenges and strategies of contemporary antiprotozoal drug research, paying the due attention to the already published reviews.

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First Century of Chagas' Disease: An Overview on Novel Approaches to Nifurtimox and Benznidazole Delivery Systems

Cited by 68 publications

References 42 publications

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Promising Efficacy of Benznidazole Nanoparticles in Acute Trypanosoma cruzi Murine Model: In-Vitro and In-Vivo Studies

Pharmacokinetics and Tissue Distribution of Benznidazole after Oral Administration in Mice

New Chemotherapeutic Strategies Against Malaria, Leishmaniasis and Trypanosomiases

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