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Multi-user Equipment approved in grant 2019/17913-5: Thermogravimetric Analyzer TGA 4000

Abstract

Candida albicans is the most prevalent yeast in vulvovaginal candidiasis (VVC) episodes. Currently, the available therapy for this infection involves the administration of drugs, however, several resistance cases has been observed. Due to these factors, the search for new sources of antifungal molecules, among them, the natural products derivatives is in expansion. The hypericin (HIP) is a substance obtained from Hipericum perfuratum, which has been promising biological effects, among them the antifungal. However, due to physicochemical characteristics, such as the low aqueous solubility under acidic and physiological pH conditions, fast hydrolysis at alkaline pH and light instability can difficult their use, resulting in pharmacokinetic restrictions, as low absorption in oral route and extensive hepatic metabolism. Thus, nanotechnological strategies such as the incorporation of HIP in nanostructured lipid carriers (CLNs) dispersed in thermoresponsive hydrogels (HG) for vaginal administration proves to be an interesting option to facilitate their use, since can promote drug protection against degradation and increase the permanence in the administered site. In addition, vaginal administration may be advantageous since the vaginal mucosa has high permeability, high blood supply and absence of first-pass metabolism, optimizing the local action. This work aims the pharmacotechnical development and the study of in vitro and in vivo anti-Candida albicans activity of HG-dispersed CLNs for vaginal administration of HIP. The HIP containing CLNs will be characterized by the determination of the hydrodynamic particle diameter, polydispersity index, Zeta potential, transmission electron microscopy, low-angle X-ray scattering, and encapsulation efficiency of HIP. For HG, differential exploratory calorimetry, rheology, in vitro mucoadhesion and syringability analyzes will be employed. Additionally, an analytical methodology will be developed and validated for HIP quantification by HPLC followed by studies of release, permeation, and in vitro retention of the formulations. In vitro biological assays of antifungal activity will be performed using C. albicans strains and cytotoxicity assays in keratinocyte cell lines. Finally, an in vivo experimental evaluation will be performed using a VVC model. In resume, it is expected to have a system that has potential for vaginal administration of HIP, bringing new perspectives for VVC treatment. (AU)

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VEICULO: TITULO (DATA)
VEICULO: TITULO (DATA)