Preparation, Physicochemical Characterization, and Stability Study of Lippia origanoides Essential Oil-based Nanoemulsion as a Topical Delivery System

Introduction: Fungal diseases are a priority in research, development, and health care, according to the WHO, mainly due to Candida spp. Essential oils (EOs) of the genus Lippia have demonstrated broad antimicrobial biological activity. Previous studies identified the anti-Candida potential of a thymol/p-cymene chemotype EO from Lippia origanoides H.B.K coded “0018”. Nanoemulsions favor the biological activity of EOs and overcome limitations such as low solubility, instability against oxidizing agents, pH, light, and low permeability. To develop, characterize, and adjust a prototype of an O/W nanoemulsion containing the "0018” EO from Lippia origanoides for its evaluation in an in vitro permeability study. Methods: Nanoemulsions were obtained using a high energy high shear method. Their particle size distribution, Z potential, viscosity, pH, encapsulation efficiency (EE), thermodynamic stability and the Turbiscan Stability Index (TSI) were evaluated. The nanoemulsion prototype was adjusted to improve performance characteristics and microbiological efficacy. Thymol was used as an analyte in the EO quantification using UHPLC-DAD. Results: An O/W nanoemulsion with hydrodynamic diameter <200 nm and polydispersity index <0.3, EE >95%, with TSI < 1.5, anti-Candida albicans efficiency >95% was obtained; permeable with a flow of 6.0264 μg/cm²/h and permeability coefficient of 1.3170x10^-3 cm/h. Conclusion: A pharmaceutical formulation prototype is obtained that maintains the physical and physicochemical characteristics over time. Permeability is verified in an in-vitro model. It is proposed to evaluate its antifungal activity in preclinical or clinical studies as a contribution to the treatment of topical fungal diseases caused by Candida spp., through the use of biological resources and Colombian biodiversity.