*Article* **Tailoring of Geranium Oil-Based Nanoemulsion Loaded with Pravastatin as a Nanoplatform for Wound Healing**

**Waleed Y. Rizg 1,2 , Khaled M. Hosny 1,2,\*, Bayan A. Eshmawi <sup>1</sup> , Abdulmohsin J. Alamoudi <sup>3</sup> , Awaji Y. Safhi <sup>4</sup> , Samar S. A. Murshid <sup>5</sup> , Fahad Y. Sabei <sup>4</sup> and Adel Al Fatease <sup>6</sup>**


**Abstract:** The healing of a burn wound is a complex process that includes the re-formation of injured tissues and the control of infection to minimize discomfort, scarring, and inconvenience. The current investigation's objective was to develop and optimize a geranium oil–based self-nanoemulsifying drug delivery system loaded with pravastatin (Gr-PV-NE). The geranium oil and pravastatin were both used due to their valuable anti-inflammatory and antibacterial activities. The Box–Behnken design was chosen for the development and optimization of the Gr-PV-NE. The fabricated formulations were assessed for their droplet size and their effects on the burn wound diameter in experimental animals. Further, the optimal formulation was examined for its wound healing properties, antimicrobial activities, and ex-vivo permeation characteristics. The produced nanoemulsion had a droplet size of 61 to 138 nm. The experimental design affirmed the important synergistic influence of the geranium oil and pravastatin for the healing of burn wounds; it showed enhanced wound closure and improved anti-inflammatory and antimicrobial actions. The optimal formulation led to a 4-fold decrease in the mean burn wound diameter, a 3.81-fold lowering of the interleukin-6 serum level compared to negative control, a 4-fold increase in the inhibition zone against *Staphylococcus aureus* compared to NE with Gr oil, and a 7.6-fold increase in the skin permeation of pravastatin compared to PV dispersion. Therefore, the devised nanoemulsions containing the combination of geranium oil and pravastatin could be considered a fruitful paradigm for the treatment of severe burn wounds.

**Keywords:** nanotechnology; burn wound; ex-vivo permeation; essential oil; statins; Box–Behnken design
