Summary of the model statistics.

Enteromorpha intestinalis is a green seaweed enriched with diverse bioactive compounds that possess substantial pharmacological and biotechnological properties. Despite the focus on their therapeutic applications, research on the development of nano-formulations is limited. Therefore, this study aimed to develop an E. intestinalis (EI) extract-based nanoemulsion for topical use. Olive oil, Tween-80 (surfactant), and PEG-400 (co-surfactant) were selected for the formulation of the nanoemulsion. The Smix ratio was set to 1:1 using a pseudo-ternary phase diagram. Moreover, a design experiment ascertained the composition of the formulation, followed by physicochemical characterization. The optimal formulation, based on droplet size, was selected for further analysis. Stability studies, antioxidant and anti-inflammatory properties of selected nanoemulsion formulation were determined and acute dermal toxicity assay was also performed. The best formulation (F6) displayed a droplet size of 183.27 ± 20.04 nm, PDI of 0.6, and viscosity of 290 ± 5.77 m-Pa.S. The developed nanoemulsion exhibited good skin compatibility and a slightly acidic pH. Both the extract and nanoemulsion formulation exhibited concentration-dependent antioxidant activity. The nanoemulsion had a lower IC50 value of 163.19 μg/mL, showing greater efficacy than the seaweed extract alone. Formulation (F6) also significantly (p E. intestinalis extract. This advancement paves the way for further in vivo studies to assess the efficacy and safety of this formulation for clinical applications.