Tinea is a common superficial infection caused by keratinophylic fungi called dermatophytes. The objective of the current investigation was to develop and optimize a self-nanoemulsion drug delivery system (SENDDs) using clove oil loaded with naftifine (NF). Clove oil possesses good anti-inflammatory and antifungal properties that can support naftifine action. Box-Behnken designs were used to prepare plain and naftifine loaded SENDDs. The plain SENDDs were evaluated for their globule size. The medicated formulations (NF-CO-SENDDs) were characterized by measuring their globular size, ex vivo % NF permeated, level of interleukin-31 in rats, and antifungal activity. The optimum clove oil level was found to be 10-17%, while NF-CO-SENDDs formulations displayed globular sizes ranging from 119 to 310 nm. The statistical design confirmed the synergistic effect of clove oil and NF in the treatment of fungal infections, confirming that the anti-inflammatory effect of clove oil can counteract the side effects of NF. The optimized formulation composed of 14% clove oil, 12.5 mg Naftifine, and prepared with an Smix ratio equaling 3:1, exhibited good antifungal and anti-inflammatory activity, achieving up to 2-, 3-, 5.75-, and 2.74-fold increases in the amount of permeated NF, steady-state flux, permeability, and diffusion coefficients, respectively, compared with a commercial product. Moreover, the optimum formulation revealed an adequate zeta potential value of 28.31 ± 1.37 mV and showed reasonable stability with no or mild signs of skin sensitivity. Therefore, the designed nanoemulsions containing a combination of clove oil and naftifine could be considered promising delivery systems for the treatment of tinea.
Keywords: Box–Behnken; Nanoemulsion; clove oil; experimental design; naftifine; tinea.