Effects of benznidazole:cyclodextrin complexes on the drug bioavailability upon oral administration to rats

Leonardi, Darío; Bombardiere, Maria Eugenia; Salomón, Claudio J.

doi:10.1016/j.ijbiomac.2013.10.007

Cited by 53 publications

(33 citation statements)

References 29 publications

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“…This result may suggest that BNZ-nps improve the absorption of BNZ and, therefore, its inhibitory activity against these infected cell lines. 20,21 In contrast, a lower inhibitory activity against the infected cells in both cell cultures was observed when the assay was performed using 10 μg/mL of BNZ-nps. However, taking into account the reported adverse effects of BNZ on infected patients, these results are remarkably important in terms of a potential reduction of the BNZ dose up to 25 μg/mL without losing its efficacy.…”

Section: Resultsmentioning

confidence: 88%

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: Resultsmentioning

confidence: 88%

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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“…According to Bulffer et al, young rats displayed higher BNZ levels and longer BNZ persistence times in plasma than did adults (15). Differences in BNZ pharmacokinetic parameters and biodistribution may be related also to the formulation used (13,14,17).…”

Section: Discussionmentioning

confidence: 99%

“…However, several methods have been described for BNZ quantification in animal and human plasma, urine, and milk (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22). To evaluate BNZ biodistribution, a bioanalytical method was developed to determine its quantification in mouse tissues, including spleen, brain, heart, colon, liver, lung, and kidney.…”

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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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“…Se han analizado varias estrategias para solucionar este inconveniente, pues este aspecto farmacocinético incide directamente en las dosis que deben ser administradas y, consecuentemente, con la adherencia al tratamiento y la aparición de efectos adversos dependientes de la dosis (33) .…”

Section: Efectos Adversos Del Tratamientounclassified

Tripanosomiasis americana, una mirada desde el tratamiento

et al. 2016

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ResumenLa tripanosomiasis americana o enfermedad de Chagas es una infección parasitaria causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. La quimioterapia, adicional a un control oportuno de vectores y rigurosidad en el control de las transfusiones, son los elementos más importantes para el manejo de esta parasitosis. En la actualidad, el mercado farmacéutico solo ofrece nifurtimox y benznidazol como opciones terapéuticas, y a pesar de que se han obtenido resultados satisfactorios con el uso de estos medicamentos en fases agudas de la enfermedad, tripanosomiasis congénita y accidentes de laboratorio, la efectividad en las fases crónicas es notoriamente menor. Además, ambos fármacos generan ciertos efectos adversos que deben ser tenidos en cuenta por el personal de la salud, antes de iniciar el debido manejo de esta enfermedad. El objetivo del presente artículo es revisar el estado actual del tratamiento farmacológico de la tripanosomiasis americana, buscando resumir los nuevos avances terapéuticos y dar a conocer las limitaciones de los mismos debido a sus efectos adversos. Palabras clave. Enfermedad de Chagas; Tripanosomiasis; Terapéutica. Abstract American trypanosomiasis or Chagas disease is a parasitic infection caused by the flagellate parasite Trypanosoma cruzi, whose main vector is an insect of the Hemiptera class, called triatomine. Chemotherapy, in addition to an appropriate vector control and a rigorous control of transfusions, are the most important strategies for the management of this parasitosis. Currently, the pharmaceutical market only offers nifurtimox and benznidazole as treatment options, and although satisfactory results have been obtained with the use of these drugs in either acute stages of the disease, congenital trypanosomiasis and laboratory accidents, its effectiveness in the chronic phases is significantly smaller. In addition, both drugs produce some side effects that must be taken into account by health workers, before starting the proper management of the disease. The aim of this article is to review the current state of the American trypanosomiasis treatment, in order to summarize the new advances in therapeutics and to introduce their limitations due to adverse effects. Keywords. Chagas Disease; Trypanosomiasis; Therapeutics. An INTRODUCCIÓNLa tripanosomiasis americana, también conocida como enfermedad de Chagas, es la infección parasitaria más importante en las Américas, en donde afecta de 8 a 10 millones de personas (1)(2)(3) . Es causada por el parásito flagelado Trypanosoma cruzi, cuyo principal vector es un insecto de la clase hemíptera conocido como triatomino. El parási-to también puede ser adquirido por el consumo de alimentos y bebidas contaminadas, trasplantes de órganos, transfusiones sanguíneas y por vía congénita, siendo estas vías menos frecuentes (1,4) .En el curso natural de la enfermedad es posible diferenciar tres fases clínicas: una fase aguda, usualmente asintomá-tica, que t...

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Effects of benznidazole:cyclodextrin complexes on the drug bioavailability upon oral administration to rats

Cited by 53 publications

References 29 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

Tripanosomiasis americana, una mirada desde el tratamiento

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