Astaxanthin–Ascorbyl Palmitate Co-Loaded Transfersomes: Targeting Oxidative Stress and Inflammation

Astaxanthin, a potent antioxidant carotenoid, exhibits significant therapeutic potential, however its broader biomedical application is limited by chemical instability, poor aqueous dispersibility, and limited bioavailability. Lipid-based nanocarriers, particularly deformable vesicular systems such as transfersomes, offer a promising strategy to overcome these limitations. In this study, astaxanthin-loaded phosphatidylcholine transfersomes were developed using sodium deoxycholate, Tween 80, or tocopherol polyethylene glycol succinate as edge activators, in combination with either ascorbyl palmitate or sodium ascorbyl phosphate as co-antioxidants. All formulations yielded nanosized vesicles with narrow size distributions (87–124 nm) and high encapsulation efficiencies (>87%). In the optimized Tween 80-based system, the choice of co-antioxidant significantly influenced colloidal stability and astaxanthin retention, with ascorbyl palmitate preserving approximately 87% of astaxanthin after 4 weeks. The vesicles demonstrated strong radical-scavenging activity comparable to free astaxanthin and showed no cytotoxicity at physiologically relevant concentrations in NIH/3T3 fibroblasts and RAW 264.7 macrophages. Furthermore, the optimized formulations effectively reduced intracellular reactive oxygen species in human neutrophils and suppressed nitric oxide and TNF-α production in macrophages more efficiently than non-encapsulated astaxanthin. Collectively, these findings indicate that incorporation of astaxanthin with ascorbyl palmitate into deformable vesicular carriers enhances its physicochemical stability and potentiates anti-inflammatory redox activity, highlighting transfersomes as an effective platform for the delivery of redox-active carotenoids. • Stable astaxanthin transfersomes were formulated • Vesicles showed > 87% entrapment efficacy and a strong antioxidant effect • Ascorbyl palmitate improved astaxanthin retention and colloidal stability • Cytocompatibility was confirmed with NIH/3T3 fibroblasts and RAW 264.7 macrophages • Formulations reduced ROS, NO, and TNF-α in immune cells