Enhanced Anti-Inflammatory and Skin Barrier Repair Effects of Nanoemulsions Supplemented with Boesenbergia rotunda for Atopic Dermatitis.

Betamethasone dipropionate (BD) is a potent anti-inflammatory drug for atopic dermatitis (AD); however, it leads to serious adverse effects during prolonged use. We aimed to improve the biochemical properties and lower the risk of toxicity by preparing nanoemulsions containing Boesenbergia rotunda rhizome hexane extract (Hex) and essential oils (EO). Physicochemical characterization and 3-month long-term stability testing were conducted. Gas chromatography-mass spectrometry analysis was used to compare the volatile composition after nanoemulsion formulation. Further, various assays related to AD management, including antioxidant potentials, anti-inflammatory activities through inhibition of 5-lipoxygenase and cyclooxygenase-2, and nitric oxide release suppression in lipopolysaccharides-induced RAW 264.7 macrophages, were investigated. In addition, antibacterial activity against Staphylococcus aureus and cytotoxicity to RAW 264.7 macrophages and HaCaT human keratinocyte cells were also evaluated. Monodispersed nanoemulsions (<20 nm) were successfully generated by an ultrasound-assisted method. BD was successfully encapsulated into B. rotunda-based nanoemulsions with more than 95% encapsulation efficiency (EE). The major phytochemicals present in EO and Hex remained after nanoemulsion formulation. The nanoemulsions were compatible with skin pH (5.2-5.8) and exhibited stability with respect to particle size, polydispersity index, transmittance, pH, and EE when stored for 3 months at -20 °C. The BD nanoemulsions loaded with B. rotunda exhibited antioxidant activities and significantly increased the 5-lipoxygenase inhibitory activity. Furthermore, the suppression of nitric oxide release was remarkably enhanced, whereas lower cytotoxicity was observed. The BD nanoemulsions improved the level of involucrin and filaggrin in HaCaT cells, implying their valuable property for skin barrier repair. The formulation of BD into nanoemulsions also enhanced S. aureus inhibition. Either B. rotunda nanoemulsions loaded with or without BD show promise for the topical treatment and prevention of AD.