Optimization of menthol-loaded nanocapsules for skin application using the response surface methodology

Menthol is used as a natural coolant in numerous consumer healthcare products. However, low aqueous solubility and high volatility limit its applications. This study aimed to encapsulate menthol in lipid-core nanocapsules by using a nanoprecipitation method and to explore its skin application. Experiments were performed using a Box-Behnken design to investigate the influence of relevant causal parameters (weight proportions of menthol, poly(e-caprolactone) and poloxamer 188) on responses, including the hydrodynamic diameter, zeta potential and entrapment efficiency, of menthol in the nanocapsules. The optimized nanocapsules with good physicochemical features consisted of 150 mg menthol, 84 mg poly(e-caprolactone) and 125 mg poloxamer 188. The menthol-loaded nanocapsules were subsequently characterized in terms of physicochemical properties, skin localization and permeation, irritation potential and cytotoxicity. Nile Red-labelled nanocapsules supported rapid ex vivo skin penetration. Hair follicle and trans-epidermal routes played an important role in the rapid percutaneous absorption of menthol. Hen's egg chorioallantoic membrane results and cytotoxicity analysis in HaCaT and human dermal fibroblast cells suggested the safety of topically applied nanocapsules. The developed nanocapsules not only have the potential to enhance the aqueous solubility of menthol and improve the thermal stability but also are an alternative option for cosmetotextiles with fast dermal absorption properties.