Menthol-based deep eutectic systems as antimicrobial and anti-inflammatory agents for wound healing

Abstract

Effective antimicrobial treatment has been identified as a serious and unmet medical need. Herein, we present a strategy based on deep eutectic systems (DES) to overcome current limitations, answering the need not only to effectively kill bacterial agents but also to avoid their adhesion and proliferation, which is associated with biofilm formation and have a crucial impact on bacterial virulence. To achieve such a goal, natural deep eutectic systems (NADES) based on menthol (Me) and saturated free fatty acids (FFA) were produced, fully physicochemical characterized, and its bioactive properties were described. The antimicrobial potential of menthol-based NADES with FFA, namely, myristic acid (MA), lauric acid (LA), and stearic acid (SA) were investigated towards a broad panel of microorganisms. The obtained data indicates that NADES possess effective antimicrobial properties towards the Gram-positive bacterial and fungal strains tested. Among the tested formulations, Me:LA at a molar ratio of 4:1 molar was used to carry out a biofilm detachment/removal assay due to is superior microbiological properties. This formulation was able to effectively lead to biofilm removal/dispersion of not only methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans, but also Escherichia coli, without the need of any additional physical force or antibiotic. Furthermore, since microbial invasion and biofilm formation is highly undesired in wound healing, namely in chronic wound healing, the wound healing properties of these eutectic formulations was also investigated. The results suggest that these NADES can cope with microbial invasion and biofilm detachment while not compromising normal keratinocyte proliferation and migration verified in wound healing and epidermis repair, while also contributing to the reduction of cell stress and inflammation via the control of ROS production. In conclusion, these results provide the indication that NADES based on Me and FFA holds great interest as antimicrobial agents for preventive and therapeutic applications in various clinical settings, including wound healing.

Keywords: Antimicrobial; Deep eutectic systems; Fatty acids; Sustainable chemistry; Terpenes; Wound healing.