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Exp Parasitol ; 186: 24-35, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29448040

RESUMO

Amphotericin B (Amp) has been well-successfully used to treat against Leishmania infection, although high toxicity has been found in patients. In the present study, Amp was administered in Leishmania infantum-infected BALB/c mice by three distinct delivery systems aiming to compare their efficacy against challenge infection, as well as their side effects in a murine visceral leishmaniasis (VL) model. This product was administered in a Poloxamer P407 (Pluronic® F127)-based polymeric micelle system (Amp/M), in the Ambisome® formulation (Lip-Amp) or in a free format (free Amp). Glucantime® (Gluc) was used as a comparative drug. Aiming to evaluate different endpoints of the treatments, the efficacy of the compounds was investigated one and 15-days after the therapeutic regimens, determining the parasite load by a limiting dilution assay and a quantitative PCR (qPCR) technique, as well as evaluating the immune response generated in the infected and treated animals. In the results, Amp/M or Lip-Amp-treated mice presented the best outcomes, since significant parasite load reductions were found in the evaluated organs, as well as a parasite-specific Th1 immune response was observed in the animals. In addition, no hepatic or renal damage was found in these mice. On the other hand, free Amp or Gluc induced toxicity in the animals, which was associated with a low Th1 immune response. Comparatively, Amp/M was the most effective drug in our experimental model, and results showed that the Amp-carrying system could be considered as a future alternative in studies against VL.


Assuntos
Anfotericina B/administração & dosagem , Antiprotozoários/administração & dosagem , Sistemas de Liberação de Medicamentos/normas , Leishmaniose Visceral/tratamento farmacológico , Anfotericina B/toxicidade , Animais , Antiprotozoários/toxicidade , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Rim/efeitos dos fármacos , Leishmania infantum/efeitos dos fármacos , Fígado/efeitos dos fármacos , Meglumina/administração & dosagem , Antimoniato de Meglumina , Camundongos , Camundongos Endogâmicos BALB C , Micelas , Nitritos/metabolismo , Compostos Organometálicos/administração & dosagem , Organismos Livres de Patógenos Específicos , Baço/citologia , Baço/imunologia
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