Desenvolvimento de um hidrogel termorresponsivo contendo o extrato das cascas do caule de Commiphora leptophloeos com potencial aplicação no tratamento de candidíase vulvovaginal
Commiphora leptophloeos (Mart.) J.B. Gillett. (Burseraceae) is a medicinal plant native to the Caatinga biome, popularly used to treat gynecological infections. The present work aimed to characterize the chromatographic profile and marker content of the C. leptophloeos stem bark extract, and to eval...
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| Formato: | doctoralThesis |
| Idioma: | pt_BR |
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Universidade Federal do Rio Grande do Norte
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| Endereço do item: | https://repositorio.ufrn.br/handle/123456789/58232 |
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| Resumo: | Commiphora leptophloeos (Mart.) J.B. Gillett. (Burseraceae) is a medicinal plant native to the Caatinga biome, popularly used to treat gynecological infections. The present work aimed to characterize the chromatographic profile and marker content of the C. leptophloeos stem bark extract, and to evaluate its toxicity and antifungal and antibiofilm potential against Candida spp., through pre-clinical tests in vitro and in vivo. The study also aimed to develop a new thermoresponsive hydrogel containing C. leptophloeos extract. The hydrogel was developed by incorporating the extract (4%) into a hydrogel formulation based on chitosan (1.0%) and poloxamer 407 (18%), and evaluated using physical (organoleptic characteristics, rheological tests and texture profile analysis), chemical (proanthocyanidin content and pH) and microbiological parameters. Under the conditions of the study, the extract and hydrogel showed good physicochemical and microbiological stability for 3 months at 25 °C ± 2 °C and 60% ± 5% relative humidity (RH). In addition, the phytochemical analyses carried out by liquid chromatography and mass spectrometry and by chemical tests enabled the annotation and quantification of the total proanthocyanidin content in the extract (230.38 mg/g of extract) and per gram of hydrogel (135.23 mg of proanthocyanidin/g of hydrogel). Additionally, the hydrogel had an appearance, colour and odour characteristic of the extract, a pH close to 4.5, compatible with the vaginal environment, and a sol-gel transition temperature close to body temperature (35 °C). The toxicity of the extract and hydrogel were assessed in vitro by the haemolytic activity and cytotoxicity tests on uterine/endometrial epithelial cells (HEC-1A), and in vivo by the acute toxicity test on the alternative Galleria mellonella model. In all tests, the free extract and the hydrogel formulation proved to be biocompatible, since they did not cause cytotoxicity in human erythrocytes and HEC-1A cells, and no signs of acute toxicity and mortality were observed in G. mellonella larvae. In vitro antifungal and antibiofilm efficacy was evaluated against reference strains of Candida spp. and clinical isolates (including fluconazole-resistant strains) obtained from blood cultures of patients with candidaemia and vaginal secretions of patients with vulvovaginal candidiasis. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were determined using the microdilution technique, and biofilm inhibition was assessed using the crystal violet and XTT assays. The synergistic effect of the extract in combination with fluconazole was determined using the checkerboard method. The extract showed antifungal activity with MIC values ranging from 2,500 to 312.5 μg/mL and significantly reduced the biofilm formed on all the Candida spp. strains investigated. Furthermore, the combined action of the extract with fluconazole produced synergistic antifungal effects against Candida spp. (IFIC=0.311.5). Furthermore, the antifungal potential of the free extract and hydrogel were evaluated in vivo in the alternative model of C. albicans infection in G. mellonella. The hydrogel containing the extract showed greater antifungal potential than the free extract at all concentrations tested, and in the survival assay showed high larval viability in larvae infected with C. albicans. In general, the findings of this work revealed that the antifungal and antibiofilm effect of C. leptophloeos extract was enhanced when incorporated into the hydrogel and toxicity was reduced. Finally, it can be concluded that the C. leptophloeos extract has a potential antifungal effect and can be applied as an active ingredient in the development of an herbal medicine for the treatment of fungal infections. |
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