Desenvolvimento de um hidrogel a partir da fração diclorometano de Sideroxylon obtusifolium T. D. Penn com atividade anti-candida: estudo in vitro e in vivo

Abstract

Species of Candida that are capable of causing infections have become resistant to commonly used antifungal drugs, thus, alternative medicines that are efficient against these infections seem necessary. In this way, in vitro studies have taken the lead in finding curative approaches and herbal agents have shown beneficial effects in these procedures in an attempt to develop new natural medicines that cause fewer adverse effects and are more accessible to the population. The objective of this study is to develop, characterize and biologically evaluate a hydrogel based on the dichloromethane fraction (HFDIC) of the leaf extract of S. obtusifolium T.D. Penn. (Quixabá). The methodological procedure started with the development of an Aristoflex hydrogel loaded with the dichloromethane fraction (FDIC) of the extract. In vitro tests were carried out to characterize the HFDIC through physicochemical analyses applied in pharmaceutical formulations such as: pH, resistance to centrifugation, viscosity and spreadability. The quality control of the HFDIC was carried out through the search for mesophilic and pathogenic microorganisms. The analysis of the antifungal activity of HFDIC was performed through logarithmic reduction. Acute toxicity was evaluated in vivo in Mus musculus mice. The results obtained in the experiments were analyzed with SPSS 25 and Excel software, the tests used varied according to the data distribution, at a significance level of 5%. The pH value of the HFDIC was 5.85, the formulation remained stable when subjected to extreme conditions by centrifugation. The HFDIC is characterized as a non-Newtonian fluid of the pseudoplastic type, that is, the viscosity decreases with increasing shear rate, in addition to having good spreadability. No signs of in vivo toxicity were found for HFDIC. Regarding quality control, no presence of contaminating microorganisms was observed in the formulation. FDIC significantly (p<0.05) reduced the growth of C. albicans (clinical strain) and C. glabrata (ATCC 90030) and HFDIC showed potentially antifungal activity on these species with visual reduction in colony counts. It is concluded that the hydrogel loaded with the dichloromethane fraction (HFDIC) has physicochemical properties of pH, resistance to centrifugation, viscosity and permissible spreadability for a drug for topical application in the oral mucosa. HFDIC did not produce signs of toxicity in Mus musculus mice. Despite being a non-sterile formulation, it was not contaminated by Escherichia coli, Staphylococcus aureus, Salmonella, Candida albicans, or by mesophilic microorganisms. HFDIC has potentially anti-Candida activity, indicating promising results regarding the possibility of a future indication and/or use of this formulation in the dental clinic for the treatment of oral candidosis.