Abstract:
: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.
journal_name
Exp Parasitoljournal_title
Experimental parasitologyauthors
Mendonça DVC,Martins VT,Lage DP,Dias DS,Ribeiro PAF,Carvalho AMRS,Dias ALT,Miyazaki CK,Menezes-Souza D,Roatt BM,Tavares CAP,Barichello JM,Duarte MC,Coelho EAFdoi
10.1016/j.exppara.2018.02.003subject
Has Abstractpub_date
2018-03-01 00:00:00pages
24-35eissn
0014-4894issn
1090-2449pii
S0014-4894(17)30307-7journal_volume
186pub_type
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