Encapsulação do diterpeno esclareol em carreadores lipídicos nanoestruturados e seu efeito sinérgico com a doxorrubicina

• Ano de defesa: 2017
• Autor(a) principal: Gabriel Silva Marques Borges
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Carrreadores Lipídicos Nanoestruturados; Esclareol; Sinergismo; Produtos Naturais; Câncer; Doxorrubicina; Produtos naturais Analise; Carreadores lipídicos nanoestruturados; Câncer Tratamento
• Link de acesso: http://hdl.handle.net/1843/BUOS-BAWJDD

Cancer is a big public health issue all over the world. The most common way to treat cancers already spread throughout the body is through chemotherapy. Due its high toxicity and resistance issues, new options for the chemotherapeutic treatment of neoplasias are required. An importante source of new compounds with therapeutic activity is the Vegetal Kingdom. The diterpene sclareol, first isolated from Salvia sclarea, is a molecule that is arousing interest due its cytosatatic and cytotoxic activities in several cancer cell lines. Its hydrophobicity, however, is a limiting factor for its in vivo administration. Trying to solve this issue, sclareol was loaded in Nanostrucured Lipid Carriers (NLC), what would allow its in vivo administration in higher doses. The in vitro cytotoxicity of the sclareol and the sclareol loaded NLC was evaluated in two human tumour cell lines: MDA-MB-231 (breast adenocarcinoma) and HCT-116 (colon carcinoma). It was observed that, when loaded in NLC, the cytotoxicity of sclareol is diminished in both cell lines. Moreover, for the HCT-116 cell line, the sclareol produced subdiploid content when not enpasulated, but when in NLC, it produced cell cycle arrest in the G2/M checkpoint. This can be an indicative of a different cell death mechanism induced by the sclareol loaded NLC, what could explain the smaller cytotoxicity of them. In that way, the NLC are an alternative for the veiculation of sclareol, but seem to reduce its activity. Hence, new NLC were produced, loading sclareol and also a well-known anticancer drug, doxorubicin. NLC containing doxorubicin (0,05% w/v) and two different concentrations of sclareol (0,05 and 0,2% w/v) were produced. The doxorubicin and sclareol loaded NLC had appropriate size, narrow size distribution and could control the release of doxorubicin in PBS medium pH 7,4. Moreover, the sclareol was loaded more efficiently in the concentration of 0,05% w/v and there was seen a synergism between the molecules in the NLC that were loading 0,05% w/v of sclareol, in the cancer cell line MDA-MB-231. Therefore, the NLC are an option to deliver, simultaneously, sclareol and doxorubicin and, moreover, the loading of doxorubicin and sclareol leads to a synergism between the molecules, being a promising alternative for the treatment of cancer.