A high-energy ultrasonication strategy for the development and stabilization of astaxanthin nanoemulsions: formulation optimization and antioxidant evaluation

Astaxanthin (AXT), a xanthophyll carotenoid with strong antioxidant and therapeutic potential, faces limitations in clinical applications due to its poor solubility, instability, and low oral bioavailability. This study aimed to enhance AXT's solubility, stability, and biological activity through nanoemulsion formulation. Olive oil was selected as the lipid phase, while Tween 80 and sodium caseinate served as surfactant and co-surfactant, respectively. Nanoemulsions were prepared using high-energy ultrasonication, and pseudo-ternary phase diagrams guided the optimization of Smix ratios and oil-to-Smix compositions. Two optimized formulations, NE2 and NE6, exhibited nanometer droplet sizes (24.13 nm and 11.88 nm), narrow PDI (<0.28), and high negative zeta potentials (-39.20 mV and -34.60 mV), confirming good colloidal stability. Both formulations showed over 91% drug content and more than 73% entrapment efficiency. <i>In vitro</i> release studies revealed significantly improved dissolution, with NE2 achieving 78.61% release at 240 min. Antioxidant assays (DPPH) indicated strong radical scavenging activity, with NE2 showing slightly higher potency. Stability tests demonstrated that NE2 offered superior release and antioxidant activity, while NE6 ensured better long-term stability. Overall, ultrasonicated nanoemulsions proved to be an effective strategy for improving AXT delivery in pharmaceutical and nutraceutical applications.