Vulvovaginal candidiasis (VVC) is a fungal infection caused by Candida albicans. The treatment of choice involves antifungal administration of topical or systemic use, for which it has observed numerous cases of antifungal resistance. Thus, many researchers are working diligently on the use of alternative methods, such as photodynamic therapy (PDT) and the discovery of substances, among them those from natural sources who may have therapeutic benefit in the treatment of VVC, as hypericin (HIP), obtained from Hypericum perforatum, which has shown antifungal action, this effect being enhanced by the use of PDT, because it acts as photosensitizer. However, its clinical use faces many challenges, mainly due to its physico-chemical characteristics such as low aqueous solubility in conditions of acid and physiological pH, rapid hydrolysis at alkaline pH and instability in the presence of light, resulting in pharmacokinetic restrictions such as low oral absorption, extensive hepatic metabolism and rapid elimination. Therefore, its incorporation into carrier lipid nanostructured (NLCs) dispersed in hydrogels (HG) for in situ gelation for vaginal administration may to be an interesting option to enable its use, associated or not to PDT, since these systems can protecting the drug from degradation and increase the formulation residence time in the vaginal environment, allowing drug controlled release in the specific site of action. Furthermore, the vaginal administration can be advantageous since the vaginal mucosa has high permeability, high blood supply and absence of first-pass metabolism, optimizing its local action. The NLCs plus HIP will be characterized using average hydrodynamic diameter of analysis and polydispersity, zeta potential, atomic force microscopy and HIP encapsulation efficiency. HG will be characterized using differential scanning calorimetry analysis, rheology and texture profile and in vitro mucoadhesion . It will be developed and validated analytical methodology for quantification of HIP by HPLC and performed release, permeation and retention in vitro studies of formulations. They will be conducted biological assays in vitro antimicrobial activity employing strains of C. albicans and cytotoxicity in keratinocytes. Finally, the formulations will be carried out tests in vivo model of VVC.
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