Avaliação da toxicidade aguda de lipossomas contendo tártato emético para tratamento da leishmaniose e validação de método por espectrometria de absorção atômica para doseamento de antimônio.

• Ano de defesa: 2021
• Autor(a) principal: Larissa Dutra Coelho
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; Brasil; FARMACIA - FACULDADE DE FARMACIA; Programa de Pós-Graduação em Ciências Farmacêuticas; UFMG
• Palavras-chave em Português: Lipossomas; Tártaro emético; Leishmaniose visceral; Toxicidade aguda; Espectrometria de absorção atômica
• Link de acesso: http://hdl.handle.net/1843/40508

Bioactive substances based on trivalent antimony, including tartar emetic (TE), were the first class of compounds used in the treatment of schistosomiasis and leishmaniasis. However, its use has been discontinued due to its low therapeutic index and its adverse effects such as thrombocytopenia and electrocardiogram disturbances. The use of liposomes has shown to be a promising strategy for the delivery of bioactive substances in the region of interest and for the reduction and/or elimination of undesirable effects. Development of new pharmaceutical products requires carrying out of pre-clinical studies of acute toxicity and biodistribution, which makes it possible to verify regions of accumulation of bioactive substances and elimination pathways. This information makes possible to infer on targets of therapeutic activity and toxicity. Therefore, the objective of this work was to evaluate the acute toxicity and validate the atomic absorption spectrometry method for further study of in vivo biodistribution of TE-containing liposomes. For the study of acute toxicity, healthy mice treated with free TE or liposome containing TE (Lip-TE) in a single dose of 16 mg/kg Sb3+ intravenously, and followed for 14 days. Death of two animals in free TE treated group and no death in the Lip-TE treated group was observed. After 14 days, the animals were euthanized, blood and organs collected for hematological, biochemical and histopathological exams. A superior liver and cardiac toxicity was observed in animals treated with TE when compared to animals treated with Lip-TE, Lip-Blank and PBS. A simple analytical method also developed to determine the total concentration of antimony (Sb) in healthy mice hearts by graphite furnace atomic absorption spectrometry (GFAAS), after acid digestion with 65% nitric acid (v/v). The method was validated following procedures and acceptability criteria required by INMETRO (DOQ-CGCRE-008). The method showed matrix effect and linearity in the concentration range of 20 µg/L and 100 µg/L. The detection and quantification limits were 20.1 µg/L and 31.5 µg/L, respectively. Repeatability and precision were evaluated by fortifying the samples at known concentrations of antimony, with recovery between 92% and 105%. It was possible to conclude with this work that Lip-TE was able to reduce the systemic toxicity of TE and also that the analyzed analytical parameters demonstrated that the method developed to determine the concentration of Sb in heart of mice by GFAAS produces satisfactory results.