Preparation, characterization, ex vivo transdermal properties and skin irritation evaluation of 1,8-cineole nanoemulsion gel.

1,8-cineole (1,8-CIN) is a monoterpene that has significant inhibitory effects on dermatophytes. However, its volatile and difficult to stay in the skin have been the major limitation against its use. The aim of this study was to increase the deposition amount of 1,8-CIN in the skin and enhance its targeting to the skin surface. In the present study, 1,8-cineole nanoemulsion (1,8-CIN-NE) was prepared by the Water Titration method. Then, 1,8-cineole nanoemulsion gel (1,8-CIN-NG) was prepared by mixing 1,8-CIN-NE with gel substrates. Finally, its characterization, stability, in vitro antifungal activity, skin irritation, and transdermal properties were evaluated. The optimal 1,8-CIN-NG was around 21 nm in size with a high degree of monodispersity and the nanoemulsion droplets were surrounded by gridded gel substrates. 1,8-CIN-NG maintained excellent stability under various conditions and had no skin irritation. 1,8-CIN-NG had a significant inhibitory effect on dermatophytes. Nanoemulsion gel (NG) increased the deposition of 1,8-CIN in the skin. The histopathological evaluation indicated that 1,8-CIN-NG treatment group showed less morphological changes in the skin than the 1,8-CIN-NE or 1,8-CIN alone groups. This result is consistent with the results of the skin irritation test slight, indicating that 1,8-CIN-NG is a safe topical preparation. These results suggested that 1,8-CIN-NG can be used as an efficient agent to manage dermatophytes infections.