Detalhes bibliográficos
Ano de defesa: |
2023 |
Autor(a) principal: |
Rebouças, Louhana Moreira |
Orientador(a): |
Não Informado pela instituição |
Banca de defesa: |
Não Informado pela instituição |
Tipo de documento: |
Tese
|
Tipo de acesso: |
Acesso aberto |
Idioma: |
por |
Instituição de defesa: |
Não Informado pela instituição
|
Programa de Pós-Graduação: |
Não Informado pela instituição
|
Departamento: |
Não Informado pela instituição
|
País: |
Não Informado pela instituição
|
Palavras-chave em Português: |
|
Link de acesso: |
http://www.repositorio.ufc.br/handle/riufc/69962
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Resumo: |
Betulinic acid is a promising antineoplastic agent as a selective chemotherapy, however it has low solubility in water, which makes its delivery difficult in aqueous systems. Some substances may potentiate the antitumor efficacy of antineoplastic agents, an example is hesperidin. One strategy for delivering these assets is to carry them in the form of microcapsules. The objective of the present work is to develop microcapsules based on polysaccharides, guar gum, sodium alginate for the coencapsulation of hesperidin and betulinic acid for antitumor application against promyelocytic leukemia. Microcapsules were formulated with sodium alginate and with alginate crosslinked with Ca+2 ions. Microcapsules were also formulated containing the active ingredients in a nanoemulsion based on linseed oil in a polysaccharide solution for subsequent drying. The microcapsules were prepared by spray drying technique and characterized by FTIR (Fourier Transform Infrared Spectroscopy), SEM (Scanning Electron Microscopy), DSC (Differential Scanning Calorimetry) and XRD (X-ray Diffraction). Encapsulation Efficiency (EE) was determined. A kinetic study of the simultaneous release of betulinic acid and hesperidin from the microcapsules was performed. The in vitro cytotoxicities against the tumor cell line HL-60 (promyelocytic leukemia) and non-tumor L-929 (murine fibroblast) were evaluated by the MTT (3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide) assay. To assess non-clinical safety in vivo, acute toxicity was determined and locomotor activity was evaluated in zebrafish (Danio rerio). The results showed that the formulated microcapsules presented EE between 65.15% and 99.76%. The microcapsules obtained by drying the nanoemulsion were amorphous and predominantly spherical. In the controlled release study, the mathematical model of Korsmeyer-Peppas was used to explain the release mechanism of the microcapsules classified as Super Case II. The increase in the cytotoxic effect of betulinic acid when associated with hesperidin against the HL-60 cell line was proven and also showing in the microcapsules a decrease in the cytotoxic effect of betulinic acid against non-tumor cells when compared to the free actives. The microcapsules were considered safe, as they did not alter the locomotor system and were not toxic to adult zebrafish. Therefore, the microcapsules obtained showed promise in the treatment of promyelocytic leukemia. |