Avaliação de hidrogel incorporado ao citral aplicado ao tratamento de candidose bucal

Abstract

Oral candidiasis is a frequent disease in immunosuppressed patients and users of removable dentures, caused by fungi that have shown resistance to drugs available on the market and a high rate of recurrence. In this context, the search for new therapeutic alternatives is highlighted, such as the use of terpenes such as citral, which has properties of pharmacological interest. This study evaluated in silico and in vitro the antifungal activity of citral isolated on Candida ssp and incorporated into a hydrogel, as well as analyzed the physicochemical, antifungal and toxicological properties of this hydrogel. Strains were used: C. albicans ATCC 10231, C. glabrata ATCC 90031, C. krusei ATCC 6258, C. tropicalis ATCC 750 and clinical strains of C. albicans A4, C. albicans A5 and C. albicans A6. Through the in silico assay, the biological potential of the monoterpene, its theoretical oral bioavailability and acute oral toxicity were evaluated. The Minimum Inhibitory Concentration (MIC), Minimum Fungicidal Concentration (MFC) and its effect on the growth kinetics of C. albicans were determined. As well as its mechanism of action on the biosynthesis of the fungal cell wall and membrane. The physicochemical properties of the hydrogel incorporated into citral (HC) were determined by means of ph, resistance to centrifugation, viscosity and spreadability. The HC microbial susceptibility was verified by the agar disk-diffusion test. Acute oral toxicity and clastogenic and aneugenic potential were evaluated in Mus musculus mice (2000mg/kg). Data were analyzed using descriptive and inferential statistics. In silico assays demonstrated that citral has a broad spectrum of action on microorganisms of great clinical importance. Citral MIC ranged from 62.5 µg/mL to 250 µg/mL and was classified as a fungicidal agent. Citral had a potentially significant effect on the growth kinetics of C.albicans (p<0.05). The likely mechanism of action interfered with the plasma membrane through interaction with ergosterol. The HC had an acidic pH, good stability and spreadability, as well as good viscosity. HC showed inhibition halos greater than or equal to 10 mm in diameter depending on the concentration analyzed, for all Candida strains tested. The product significantly inhibited the growth of C.albicans at all different concentrations evaluated, between 15 and 120 minutes, when compared to the growth control. HC did not induce signs of acute toxicity in mice submitted to gavage treatment at a single dose of 2000 mg/kg and produced a statistically significant smaller number of micronuclei compared to the positive control (50 mg/kg cyclophosphomide) in mouse erythrocytes. Citral has been shown to be a potential antifungal agent against Candida species, both as an isolated compound and incorporated into the hydrogel. HC showed low toxicity and mutagenicity, being promising for the treatment of oral candidosis.