*3.3. Formulation of Optimized FS-NTF and FS-NTF-Loaded Hyaluronic Acid Hydrogel*

Finally, the optimized nanotransfersome formulation was developed with the use of lecithin (level: −0.99 ≈ −1) 75 mg, fluconazole (level: 0.32 ≈ 0.3) 60 mg, and sesame oil (level: +0.99 ≈ 1) 75 mg. The predicted and observed values for the responses of the optimized formula are summarized in Table 7 as suggested by the software based on an analysis of the actual and predicted data. Values of the expected and adjusted R<sup>2</sup> of the studied responses were in close agreement, proving the significance and predictive capacity of the design. Moreover, the experimental and predicted ratios with a percentage error of less than 10% and acceptable residuals were found between the real and predicted responses, showing a lack of curvature in the responses and the validity of the model (Table 5).

Hyaluronic acid, a natural biomolecule, has shown its antimicrobial effectiveness against bacteria and fungi in a dose-dependent manner [30]. Another contemporary study revealed a fungistatic role of hyaluronic acid through its inhibitory effect on the fungal lysozyme and peroxidase system [11]. Further, hydrogel containing hyaluronic acid has an effective and safe coating, facilitating the proliferation of basal keratinocytes and promoting reepithelialization. This role of hyaluronic acid controls the hydration of ulcer tissues and also the inflammatory process [31]. Therefore, the hyaluronic acid hydrogel was formulated in the present study of the formulated FS-NTF and was incorporated to facilitate the application of the developed formulation at the oral mucosa.


**Table 7.** Composition of the actual and predicted responses of the optimal FS-NTF formulation.
