Radioprotective and wound healing potential of nanoemulsions and nanoliposomes encapsulating enriched astaxanthin extract from <i>Haematococcus pluvialis</i>

Astaxanthin (ATX) is a potent antioxidant with broad biological activities, yet its poor water dispersibility, low stability, and high cost have markedly limited its practical utilization. Recently, lipid-based nanocarriers have emerged as promising delivery systems to enhance the efficiency of bioactive compounds in skin protection. In this study, enriched ATX extract from<i>Haematococcus pluvialis</i>(ATXex) was encapsulated into nanoemulsions (NE-ATXex) and nanoliposomes (NL-ATXex) to evaluate radioprotective and wound healing effects through<i>in vitro</i>and<i>in vivo</i>studies. NE-ATXex and NL-ATXex were prepared using high-shear homogenization and thin-film hydration, respectively, each followed by ultrasonication. Their biological activities were assessed<i>in vitro</i>by measuring reactive oxygen species (ROS), DNA double-strand breaks, and dead cells after x-ray exposure, as well as by scratch wound healing assays.<i>In vivo</i>activities were further evaluated using mouse models of x-ray-induced skin damage and full-thickness excisional wounds. The results showed that nanocarrier formulations have high physical stability during storage and in culture medium. Treatment with NE-ATXex and NL-ATXex at ATX concentrations of 0.25-0.5 µg ml^-1reduced intracellular ROS levels by approximately 80%, as well as DNA damage and cell death by around 50%, compared with cells exposed to 2 Gy X-irradiation. In addition, both formulations promoted scratch wound closure, reaching approximately 60% at 24 h and over 90% at 48 h. NE-ATXex at an ATX concentration of 0.5 µg ml^-1showed notable cytoprotective effects, whereas NL-ATXex at the same concentration was more favorable for skin applications, specifically in tissue regeneration. NL-ATXex accelerated wound healing and promoted scar remodeling by regenerating hair follicles and adipocytes. Both nanocarriers enhanced skin radioprotection by reducing damage to epidermis, adipocytes, hair follicles, and sebaceous glands following cumulative X-irradiation at 30 Gy. These results highlight the skin protective potential of ATXex in lipid-based nanocarriers, supporting its promise for biomedical applications.