dc.contributorElaine Amaral Leite
dc.contributorhttp://lattes.cnpq.br/4360736205764856
dc.contributorRenata Barbosa de Oliveira
dc.contributorMônica Cristina de Oliveira
dc.contributorAlvaro Dutra de Carvalho Júnior
dc.creatorJaqueline Aparecida Duarte
dc.date.accessioned2020-07-14T23:32:25Z
dc.date.accessioned2022-10-03T23:12:09Z
dc.date.available2020-07-14T23:32:25Z
dc.date.available2022-10-03T23:12:09Z
dc.date.created2020-07-14T23:32:25Z
dc.date.issued2018-02-23
dc.identifierhttp://hdl.handle.net/1843/33787
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/3818525
dc.description.abstractNitroaromatic derivative 4-(chloromethyl)-3-nitro-N-(2-hydroxiethyl) benzamide (AANC) showed a promissor antitumor activity in solid tumors and reduced systemic toxicity. However, its low solubility in aqueous medium represents a barrier for intravenous (IV) administration. Thus, the aim of this study was to develop nanoemulsions (NE) loaded with AANC to allow its administration by IV route. NE with and without AANC (0.2 and 0.4% w/v) were prepared by the hot melt homogenization method following by ultra-sonication. NE without AANC had a diameter of 93 ± 4 nm, polidispersity index (PI) of 0.25 ± 0.03 and zeta potential of -38 ± 3 mV. The incorporation of AANC signficantly increased the globule diameter, as the concentration was increased from 0.2 to 0.4% w/v. However, the globule mean diameter of the formulations was below 175 nm, and a narrow size distribution with a PI lower than 0.3 was obtained. The concentration of AANC-loaded NE was about 1.66 and 2.50 mg/mL, for 0.2 and 0.4% w/v respectively. There were no significant variation in globule mean diameter, PI, and values zeta potential of the formulations (NE without and with AANC 0.4% w/v over 28 days of evaluation. However, significant reduction in the AANC concentration was also observed after 14 days of storage. Next, the cytotoxicity of the free AANC and the NE-AANC was evaluated by MTT assay against MDA-MB-231 cells (human breast adenocarcinoma). IC50 values obtained for free AANC (23.9 ± 3.0 μM) and NE-AANC (24.1 ± 0.4 μM) were similar, showing that the cytotoxicity of AANC was not affected by loading in NE. In order to evaluate the in vivo behavior of free AANC and NE-AANC, pharmacokinetic and biodistribution studies in murine experimental models were conducted. Similar half-life time for free AANC and NE-AANC was obtained. Biodistribution data and scintigraphic images showed a pronounced uptake in the liver, kidneys and intestine and significant accumulation in the tumor region. Tumor-to-muscle ratio was significantly higher for NE-AANC than free AANC suggesting greater specificity for the tumor region. Therefore, NE formulation can be a good strategy to the association of the AANC, and to allow its intravenous administration.
dc.publisherUniversidade Federal de Minas Gerais
dc.publisherBrasil
dc.publisherFARMACIA - FACULDADE DE FARMACIA
dc.publisherPrograma de Pós-Graduação em Ciências Farmacêuticas
dc.publisherUFMG
dc.rightsAcesso Aberto
dc.subjectCâncer
dc.subjectTumores sólidos
dc.subjectNitrocompostos
dc.subjectNanoemulsões
dc.titleNanoemulsão como potencial carreador da 4(clorometil)-3-nitro-n-(2-hidroxietil)benzamida: desenvolvimento de formulação e avaliação de parâmetros biológicos in vitro e in vivo.
dc.typeDissertação


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