Análise antifúngica do cinamaldeído após inclusão com 2-hidroxipropril-β-ciclodextrina submetidos a estabilidade acelerada

Abstract

The inherent characteristics of acrylic resin, a material commonly used for the fabrication of prostheses, along with the indiscriminate use of therapeutic drugs, favor the proliferation of opportunistic infections such as oral candidiasis. However, due to the antimicrobial resistance observed in recent years and the challenges in developing new antifungal agents, the use of synthetic products with antimicrobial activity, such as cinnamaldehyde, has become necessary. Because of its low bioavailability, instability, and sensitivity to light, moisture, and high temperatures, it is feasible to encapsulate cinnamaldehyde to improve its stability and ensure long-term release through inclusion with 2-hydroxypropyl-β-cyclodextrin (HP-β-CD). Thus, the aim of this study was to evaluate the antifungal activity of cinnamaldehyde in comparison with its inclusion complex with HP-β-CD, at different time points after accelerated stability testing. Initially, cinnamaldehyde emulsion solutions at 27 μg/mL were prepared, following previous studies, along with the inclusion complex of cinnamaldehyde (24 μL) + HP-β-CD. After solution preparation, a pilot study was conducted to determine the minimum inhibitory concentration (MIC), which established the concentration of cyclodextrin to be used. Subsequently, analyses were performed using high-performance liquid chromatography (HPLC), Fourier-transform infrared spectroscopy (FTIR), stability testing, and biofilm adhesion inhibition assays against Candida albicans and C. glabrata, evaluating initial time (T0), 30 days (T30), and 60 days (T60) under different temperature conditions. Data were tabulated and analyzed using the Shapiro–Wilk test, which confirmed normal distribution, followed by ANOVA. FTIR analysis confirmed the formation of the inclusion complex and the molecular interaction between cinnamaldehyde and HP-β-CD. Regarding the biofilm adhesion inhibition test, at T0, cinnamaldehyde and the cinnamaldehyde–cyclodextrin complex showed similar antifungal activity at all concentrations, significantly reducing fungal growth when compared with the gold standard (nystatin). After 30 days, freeze–thaw cycles maintained the antimicrobial activity of both substances, while storage at 4°C promoted fungal growth reduction at all concentrations. At room temperature (25°C), significant inhibition was observed from MIC×4, whereas at higher temperatures (40°C), inhibition occurred from MIC×2 for cinnamaldehyde and MIC×4 for the cinnamaldehyde–cyclodextrin complex. After 60 days, only higher concentrations maintained activity, with superior performance of the complex at MIC×8 at 25°C and 40°C, while cinnamaldehyde alone required MIC×10. Therefore, cinnamaldehyde complexation proved advantageous by preserving antifungal activity and reducing the deleterious environmental effects on its volatile capacity. This suggests it as a promising alternative for new therapeutic formulations of denture cleaning products, with potential to contribute to the prevention of oral candidiasis. Further studies are needed to assess clinical applicability and presentation forms of such products, seeking alternatives more stable than liquid solutions, capable of preserving antifungal activity in the long term while providing practicality in use.