1. Comparing the therapeutic efficacy of different amphotericin B-carrying delivery systems against visceral leishmaniasis
- Author
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Daniela P. Lage, Anna Letícia Teotonio Dias, Carlos Alberto Pereira Tavares, Daniel Dias, Jose Mario Barichello, Débora V.C. Mendonça, Eduardo A.F. Coelho, Carolina K. Miyazaki, Bruno Mendes Roatt, Ana Maria Ravena Severino Carvalho, Mariana C. Duarte, Vívian T. Martins, Patrícia A.F. Ribeiro, and Daniel Menezes-Souza
- Subjects
0301 basic medicine ,Drug ,media_common.quotation_subject ,030231 tropical medicine ,Immunology ,Antiprotozoal Agents ,Pharmacology ,Kidney ,Parasite load ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Immune system ,Drug Delivery Systems ,Meglumine ,Amphotericin B ,medicine ,Organometallic Compounds ,Animals ,Leishmania infantum ,Micelles ,Nitrites ,media_common ,Mice, Inbred BALB C ,Meglumine Antimoniate ,biology ,General Medicine ,biology.organism_classification ,medicine.disease ,Leishmania ,Specific Pathogen-Free Organisms ,Disease Models, Animal ,030104 developmental biology ,Infectious Diseases ,Visceral leishmaniasis ,Liver ,Toxicity ,Cytokines ,Leishmaniasis, Visceral ,Parasitology ,Female ,Spleen ,medicine.drug - 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.
- Published
- 2017