Nanossistemas de alfa-tocoferol e cinamaldeído: desenvolvimento, caracterização e atividade antimicrobiana

Abstract

Introduction: The topical use of α-tocopherol α-toc) and cinnamaldehyde (CNM) together in the oral cavity is still little explored, but it would add the antioxidant and proliferative characteristics of α-toc with the anti-inflammatory, analgesic and antimicrobial of the CNM. The encapsulation of these in nanosystems coated with chitosan can enhance their therapeutic effects, promoting mucoadhesion and better permeability. Objective: to evaluate in silico the anti-inflammatory potential of CNM and α-toc and antimicrobial potential of CNM, as well as to develop and characterize nanocapsules and nanostructured lipid carriers (CLN) with these actives and evaluate their antimicrobial potential in vitro. Methodology: The anti-inflammatory activity of CNM and α-toc and antimicrobial activity of CNM were evaluated in silico using molecular docking. Subsequently, the composition analysis of the oils was carried out using gas chromatography coupled to mass spectrometry (GC-MS). The development of the nanocapsules was carried out using the thermosensitive technique of poloxamer 407 and the particle size (D), polydispersion index (PDI) and zeta potential (PZ) were determined, as well as being submitted to infrared spectroscopy by Fourier transform (FTIR), carried out studies of properties of the sol-gel phases, stability, rheological tests and antimicrobial activity. The CLN were developed through hot emulsification followed by ultrasonic sonication, pre-formulation studies, Box-Behnken type design for selection of an optimized formulation, development and analysis of the D, PDI and PZ of the optimized formulations were carried out with CNM and α-toc, evaluating its in vitro antimicrobial activity. Results: The results demonstrated in silico, from molecular docking, a prediction of CNM and α-toc affinity for all evaluated targets, increasing the probability of success in anti-inflammatory and antimicrobial activities. GC-M revealed CNM as the main constituent of CNM oil and α-toc acetate as the main constituent of α-toc oil. In the dispersions of nanocapsules, particles with size ranging from 135.7 to 1997 nm and zeta potential with values between -3.76 to +11.1 were observed; FTIR confirmed the encapsulation of assets in dispersions; the sol-gel phase transition occurred at temperatures between 20°C and 30°C and remained in the form of a solution when stored at room temperature for a time that varied between 15.9 to 47.27 s, they also demonstrated stability in terms of pH, homogeneity , odor and coloration; in the rheological analyses, it was seen that the dispersions of nanocapsules have a pseudoplastic behavior, which facilitates their application due to the decrease in viscosity with effort, as well as, they present better antimicrobial activity in vitro than the encapsulated CNM (MIC from 3.12 μg/mL ) when compared to free CNM (MIC from 39 μg/mL) against strains of Escherichia coli, Staphylococcus aureus and Candida albicans. The pre-formulation study of the CLN allowed the analysis of variables that based the Box-Behnken type design, which provided the concentrations considered ideal for the components after statistical evaluation 25mg/ml of chitosan, 50mg/ml of precirol and 100mg/ ml of CNM and/or α-toc), in order to provide an optimized production of them. Antimicrobial assays showed increased and synergistic action of the actives encapsulated in this system (MIC from 8 μg/mL for CNM, 6 μg/mL for α-toc and 8 μg/mL for chitosan) when compared to the free forms MIC from 39 μg/mL for CNM, α-toc without activity at the highest concentration tested [50 mg/ml] and 260 μg/mL for chitosan) against strains of Escherichia coli, Staphylococcus aureus and Candida albicans. Conclusion: With this, it is seen that the actives presented in silico, in the molecular docking analysis, a prediction of CNM and α-toc affinity for all evaluated targets. It was also possible to develop both systems with good characteristics and potentiated antimicrobial activities, although the use of CLN is seen as more promising in the oral mucosa.