Utilização de nanopartículas fosfatadas como carreadores de antimônio: possíveis aplicações para o tratamento das leishmanioses

• Ano de defesa: 2016
• Autor(a) principal: Betania Mara Alvarenga
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Leishmania infantum; Nanocarreador de Sb; Nanopartículas biodegradáveis; Biologia celular
• Link de acesso: http://hdl.handle.net/1843/BUBD-AA8H2U

Pentavalent antimonials such as a Glucantime are used for treating leishmaniasis, but produce side effects, including cardiotoxicity and hepatotoxicity. In this work, we characterized the physicochemical properties of 4 phosphate-based composites (CNF0, CNF3, CNF5 and CNFT) as Sb (V) carriers for targeting macrophages. CNFs were synthesized in a liquid media and sterilized at 25 kGy before use. The physicochemical characterizations are determinate with zeta potential, conductivity, diameter, Sb content and crystallinity for each CNF. Macrophage viability and CNFs toxicity, independent of the Sb uptake, were evaluated to assess CNFs safety in visceral leishmaniasis treatment. The rate of macrophages infection caused by L. infantum was assayed in vitro by using Glucantime as a reference drug. CNFs featured negative zeta potentials (-14.7 to -19.5 mV), mean diameter was around 180 nm and a low dissolution constant in Milli-Q water (less than 0.02 mS cm-1 for CNF0, CNF3 and CNF5). CNF5 and CNFT showed crystalline characteristics and the peaks present in CNF5 resembling Mopungita, but other CNFs exhibited predominantly amorphous structures. CNFT had the highest concentration of Sb, 46.69 g mL-1. Cell viability was not affected at any CNFs concentrations tested. The associated scanning electron microscopy techniques, x-ray microanalisys and GFASS revealed the internalization of CNFs and Sb cell retention. Amastigote infection was reduced by all CNFs more efficiently than glucantime, including CNF0 (without Sb), but CNF3 was more effective. The group of infected macrophages challenged with CNF3 nitric oxide increase 2 times more than the infected macrophages only. These data indicate the potential of NPCs as Sb nanocarriers for specifically targeting macrophages and lowering Sb dosage without reducing leishmanicidal activity.