DEFAR - Departamento de Farmácia
URI permanente desta comunidadehttp://www.hml.repositorio.ufop.br/handle/123456789/530
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Item Treatment of murine visceral leishmaniasis using an 8-hydroxyquinoline-containing polymeric micelle system.(2016) Duarte, Mariana Costa; Lage, Letícia Martins dos Reis; Lage, Daniela Pagliara; Martins, Vivian Tamietti; Carvalho, Ana Maria Ravena Severino; Roatt, Bruno Mendes; Souza, Daniel Menezes; Tavares, Carlos Alberto Pereira; Alves, Ricardo José; Barichello, José Mario; Coelho, Eduardo Antônio FerrazNewtherapeutics are urgently needed to treat visceral leishmaniasis (VL). Due to the fact that drug discovery is a long and expensive process, the development of delivery systems to carry old and toxic drugs could be considered, as well as the evaluation of new molecules that have already shown to present biological activity. In this context, the present study evaluated the in vitro and in vivo antileishmanial activity of an 8-hydroxyquinoline (8-HQN)-containing polymeric micelle (8-HQN/M) system against Leishmania infantum, the main causative agent of VL in the Americas. The experimental strategy used was based on the evaluation of the parasite load by a limiting-dilution technique in the spleen, liver, bone marrow and draining lymph nodes of the infected and treated animals, as well as by a quantitative PCR (qPCR) technique to also assess the splenic parasite load. The immune response developed was evaluated by the production of IFN-γ, IL-4, IL-10, IL-12 and GM-CSF cytokines, as well as by antileishmanial nitrite dosage and antibodies production. Hepatic and renal enzymes were also investigated to verify cellular injury as a result of treatments toxicity. In the results, 8-HQN/M-treated mice, when compared to the other groups: saline, free amphotericin B (AmpB, as a drug control), 8-HQN and B-8-HQN/M (as a micelle control) showed more significant reductions in their parasite burden in all evaluated organs. These animals also showed an antileishmanial Th1 immunity, which was represented by high levels of IFN-γ, IL-12, GM-CSF and nitrite, associated with a low production of IL-4 and IL-10 and anti-Leishmania IgG1 isotype antibodies. In addition, any hepatic or renal damage was found in these treated animals. In conclusion, 8-HQN/M was effective in treating L. infantum-infected BALB/c mice, and can be considered alone, or combined with other drugs, as an alternative treatment for VL.Item Poloxamer 407 (Pluronic® F127)-based polymeric micelles for amphotericin B : in vitro biological activity, toxicity and in vivo therapeutic efficacy against murine tegumentary leishmaniasis.(2016) Mendonça, Débora Vasconcelos Costa; Lage, Letícia Martins dos Reis; Lage, Daniela Pagliara; Chávez Fumagalli, Miguel Angel; Ribeiro, Fernanda Ludolf; Roatt, Bruno Mendes; Souza, Daniel Menezes; Faraco, André Augusto Gomes; Castilho, Rachel Oliveira; Tavares, Carlos Alberto Pereira; Barichello, José Mario; Duarte, Mariana Costa; Coelho, Eduardo Antônio FerrazIn the present study, a Poloxamer 407-based amphotericin B (AmpB)-containing polymeric micelles system (AmpB/M) was employed in the treatment of Leishmania amazonensis-infected BALB/c mice. Initially, the in vitro antileishmanial activity (IC50 value) of AmpB/M and B-AmpB/M (empty micelles) against stationary promastigotes and amastigotes-like forms of the parasites was determined, and results were of 1.83 ± 0.4 and 22.1 ± 0.7 mM, respectively, for the promastigotes, and of 2.27 ± 0.5 and 33.98 ± 2.6 mM, respectively, for the amastigotes-like. The cytotoxic concentration (CC50) values of these products were also evaluated, and we found the results of 119.5 ± 9.6 and 134.7 ± 10.3 mM, respectively. With these values, the selectivity index (SI) was calculated and results were of 65.3 and 5.4, respectively, for the promastigotes, and of 59.3 and 3.96, respectively, for the amastigotes-like of the parasites. Free AmpB showed IC50 values of 1.2 ± 0.3 and 2.5 ± 0.5 mM for the promastigotes and amastigotes-like, respectively, whereas the CC50 value was of 9.5 ± 0.4 mM. The SI values of this drug were of 7.9 and 3.8, respectively, for the promastigote and amastigote-like stages of the parasites. After, animals were infected and received saline or were treated subcutaneously with free AmpB, AmpB/M or B-AmpB/M. In the results, free AmpB-treated and infected mice showed reductions in their body weight, which were associated with hepatic and renal damage; however, no organic alteration was observed in the AmpB/Mtreated animals. In addition, these animals showed significant reductions in their lesion average size and in the parasite burden in all evaluated infected tissue and organs, when compared to the other groups; as well as significantly higher levels of antileishmanial IFN-g, IL-12, GM-CSF and nitrite, which were associated with low production of IL-4, IL-10 and IgG1 isotype antibodies. In conclusion, this AmpB/M system could be considered as an alternative for future studies in the treatment of tegumentary leishmaniasis.Item An 8-hydroxyquinoline-containing polymeric micelle system is effective for the treatment of murine tegumentary leishmaniasis.(2016) Lage, Letícia Martins dos Reis; Barichello, José Mario; Lage, Daniela Pagliara; Mendonça, Débora Vasconcelos Costa; Carvalho, Ana Maria Ravena Severino; Rodrigues, Marcella Rezende; Souza, Daniel Menezes; Roatt, Bruno Mendes; Alves, Ricardo José; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antônio Ferraz; Duarte, Mariana Costa