Formulation and Optimization of a Melissa officinalis-Loaded Nanoemulgel for Anti-Inflammatory Therapy Using Design of Experiments (DoE)

This study reports the development and optimization of a <i>Melissa officinalis</i> oil-based nanoemulgel for transdermal delivery using a Design-of-Experiments (DoE) approach. A Central Composite Design (CCD) was applied to optimize Tween 80 concentration and homogenization time, resulting in a nanoemulsion with a droplet size of 127.31 nm, PDI of 17.7%, and zeta potential of -25.0 mV, indicating good colloidal stability. FTIR analysis confirmed the presence of functional groups such as O-H, C=O, and C-O-C, supporting the oil's phytochemical richness and therapeutic potential. DSC analysis revealed enhanced thermal stability and successful encapsulation, while SEM imaging showed a uniform and spherical microstructure. The drug release followed Higuchi kinetics (R² = 0.900), indicating diffusion-driven release, with the Korsmeyer-Peppas model (<i>n</i> = 0.88) suggesting anomalous transport. Antibacterial studies showed inhibition of <i>Staphylococcus aureus</i> (MIC = 250 µg/mL) and <i>Escherichia coli</i> (MIC = 500 µg/mL). In vivo anti-inflammatory testing demonstrated significant edema reduction (<i>p</i> < 0.05) using a carrageenan-induced rat paw model. These results support the potential of Melissa nanoemulgel as a stable and effective topical therapeutic for inflammatory and microbial skin disorders.