Desenvolvimento de hidrogel incorporado ao extrato de Byrsonima gardneriana (A. JUSS) para tratamento de candidose oral

Abstract

This study aimed to develop a hydrogel based on Pluronic® F127 (PF127) incorporated into the extract of Byrsonima gardneriana (A. Juss), analyzing, in silico, the theoretical toxicity and pharmacological and pharmacokinetic activities of major compounds of the extract, in vitro, physicochemical properties and anti-Candida activity of the formulations and, in vivo, acute oral toxicity and aneugenic and clastogenic potential. The in silico assay using two major compounds in the extract (L-Pyroglutamic acid and octanoic acid, ethyl ester) was performed using the PASS online, Moliispiration and ADMETsar softwares. The PF127-based hydrogel was developed in an ice bath with a concentration of 20% of the polymer (HP) and the incorporation of B. gardneriana extract (HBG). The physicochemical properties of centrifugation resistance, pH, preliminary stability, spreadability and viscosity were analyzed. The anti-Candida potential was evaluated through antifungal activity on planktonic cells of C. albicans (ATCC 10231). In addition, in vivo tests were performed with animal models through acute oral toxicity and aneugenic and clastogenic potential in mice. Data were analyzed using Mann-Whitney, Wilcoxon, Student's t and one-way ANOVA tests followed by Tukey's post-test (α = 0.05). The results showed that both compounds investigated, in silico, showed antibacterial and antifungal properties, possibly exhibiting the ability to undergo absorption through the blood-brain barrier and the human intestine. Theoretically, they are weak inhibitors of the human Ether-à-go-go-Related Gene (HERG), non-toxic by the AMES test, prone to biodegradation and with category III acute oral toxicity. Regarding the in vitro tests, when analyzing the physicochemical properties, HP and HBG did not present, after centrifugation, precipitates, phase separation, color change, odor and pH, which were, respectively, 6.7 and 5 .75. There was no statistically significant difference in spreadability or between the pH of the samples in the preliminary stability test. Furthermore, when analyzing the viscosity, HP and HBG behaved as non-Newtonian fluids. HBG showed a reduction of 3 log10 when compared to the growth control, representing a microbial reduction of 99.9% on C. albicans. As for the animal model, no signs of toxicity were observed in the macroscopic and histopathological exams, with no morbidity or mortality among the animals. In the micronucleus test, it was observed that, when comparing the HP and HBG groups, there was no statistically significant difference in the micronucleus count in erythrocytes. It is concluded that major compounds of B. gardneriana extract demonstrated possible pharmacological and pharmacokinetic properties, in addition to low theoretical toxicity. HBG showed important admissible physicochemical properties for a drug of topical application in the oral mucosa and anti-Candida albicans activity, showing no signs of acute oral toxicity in mice, in addition to suggesting the absence of aneugenic and clastogenic effects. Therefore, future research is necessary for alternative perspectives for dental use.