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| Author(s): |
Aline da Graça Sampaio
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | São José dos Campos. 2019-05-03. |
| Institution: | Universidade Estadual Paulista (Unesp). Instituto de Ciência e Tecnologia. São José dos Campos |
| Defense date: | 2019-03-28 |
| Advisor: | Cristiane Yumi Koga Ito |
| Abstract | |
The increase in the prevalence of fungal infections worldwide and the rise in the occurrence of antifungal resistance suggest that new researches for the discovery of antifungal molecules are needed. The aim of this study is to contribute to the prospection of therapeutic alternatives, evaluating nanoencapsulates of ellagic acid (NAE) for the treatment of oral candidosis. In order to reach the general aim, the following specific objectives were determined: to complex the ellagic acid in cyclodextrin at effective concentration against C. albicans; to chemically characterize the encapsulate; to test the activity of the encapsulate using an invasive candidosis in vitro model, searching for the mechanisms of action; to evaluate the activity of subinhibitory concentrations on the exoenzymes production, and adherence to epithelial cells; to evaluate the cytotoxicity of NAE in the effective treatment conditions in vitro and in vivo (Drosophila melanogaster); and to evaluate the in vivo effectiveness for the treatment of oral candidosis in murine model. The obtained data was statistically analyzed (level of significance 5%). HP-β-CD formed soluble inclusion complexes with EA. The percentage of EA/HP-β-CD was 15.25 ± 0.49%. SEM and FTIR analyses confirmed the formation of inclusion complex. AE/HP-β-CD showed the same antifungal activity of pure EA with MIC value of 25 µg/ml for C. albicans ATCC 18804 and 50 µg/ml for C. albicans SC 5314. Treatment with sub-MIC on C. albicans revealed increased MIC value in the presence of sorbitol for ATCC 18804 (50 µg/ml), suggesting activity on cell wall. Results suggest no effect on cell membrane. No effects of EA on morphogenesis and production of extracellular enzymes were detected. Protective effect of EA at 3.2, 6.4 e 32 µg/ml was observed in D. melanogaster model, resulting in survivals of 45, 33 and 34%. Low cytotoxicity was observed for concentrations of 200 and 250 µg/ml. In vivo tests in murine models indicated reduction in epithelial invasion after treatment EA/HP-β-CD for 24 and 48 h when compared to control. In conclusion, EA/HP-β-CD showed inhibitory effect on C. albicans in vitro, with low toxicity. Protective effect against fungal infection was observed in D. melanogaster model. In murine model of oral candidosis, EA/HP-β-CD reduced fungal epithelial invasion. (AU) | |
| FAPESP's process: | 16/21207-0 - Evaluation of application potential of ellagic acid nanoencapsuled in cyclodextrin for the treatment of oral candidosis |
| Grantee: | Aline da Graça Sampaio |
| Support Opportunities: | Scholarships in Brazil - Master |