Detalhes bibliográficos
Ano de defesa: |
2020 |
Autor(a) principal: |
Guerino, Bruna Costabeber |
Orientador(a): |
Ourique, Aline Ferreira |
Banca de defesa: |
Martins, Juliana Saibt,
Brucker, Natália,
Zamberlan, Alexandre de Oliveira,
Colomé, Letícia Marques |
Tipo de documento: |
Tese
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Tipo de acesso: |
Acesso embargado |
Idioma: |
por |
Instituição de defesa: |
Universidade Franciscana
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Programa de Pós-Graduação: |
Programa de Pós-Graduação em Nanociências
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Departamento: |
Biociências e Nanomateriais
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País: |
Brasil
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Palavras-chave em Português: |
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Palavras-chave em Inglês: |
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Área do conhecimento CNPq: |
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Link de acesso: |
http://www.tede.universidadefranciscana.edu.br:8080/handle/UFN-BDTD/945
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Resumo: |
Currently, it is sought to develop new pharmacological therapies for the treatment of diseases that affect the Central Nervous System, often with irreversible sequelae, such as cerebral ischemia. However, many substances with proven neuropharmacological activity, such as guanosine (GUO), are unable to perform their functions at the systemic level, as they have a metabolism and rapid release into the bloodstream when administered orally. Here, we show that the combination of GUO with scalene and the subsequent formation of a nanocomplex, first reported in the literature, can be a potential neuroprotection strategy. First, an ab initio study was carried out to simulate where the connections between the GUO and the scalene would occur, in order to understand the energy level of this new structure. Through a synthetic route, the GUO-scalene complex (GUE) it presented was produced and its formation was confirmed by nuclear magnetic resonance (NMR). Subsequently, the formation of the GUO-scalene nanocomplex (NGUE) was carried out, with a particle size of approximately 180 nm, PDI of 0.285, Zeta potential of 25.09 mV, pH of 6.9 and stability of up to 30 days at room temperature. , as demonstrated by the stability study of this formulation. The NGUE showed an antioxidant effect when tested by the DPPH method. Its biological safety was evaluated by demonstrating that it is not toxic to viable cells of hippocampus slices by MTT, differently from what was observed in the GUE, nor to cells peripheral blood mononucleated by MTT, Neutral Red and Violet Crystal methods. It was observed that NGUE helps to decrease the proliferation of human neuroblastoma tumor cells of the SH-SY5Y lineage, proven by the MTT, Neutral Red, PicoGrren and Violet Crystal methodologies. NGUE has a neuroprotective effect in an in vitro model of cerebral ischemia in slices of the hippocampus of rats and the damage caused by quinolinic acid. These results indicate a perspective of therapeutic use for the developed NGUE. |