Possibility of nanostructured lipid carriers encapsulating astaxanthin from Haematococcus pluvialis to alleviate skin injury in radiotherapy.

Purpose: The study aimed to protect patients' skin against ionizing irradiation during radiotherapy by using astaxanthin-encapsulated nanostructured lipid carriers (NLC-ATX). Materials and Methods: NLC-ATX was prepared by a combined method of hot homogenization and sonication. Cytotoxicity of NLC-ATX was evaluated by MTT colorimetric assay. The in vitro radioprotection of NLC-ATX for human fibroblast (HF) cells was investigated based on the level of ROS (reactive oxygen species), DNA damage, and cell death caused by X-irradiation. In addition, the in vivo radioprotection was evaluated based on the appearance and histological structure of the irradiated skin. Results: NLC-ATX was successfully prepared, with a mean particle size, zeta potential, and encapsulation efficiency of 114.4 nm, -34.1 mV, and 85.67% respectively. Compared to the control, NLC-ATX, at an optimum ATX concentration under in vitro condition, reduced the amount of generated ROS and DNA damage of 81.6% and 41.6%, respectively after X-radiation, resulting in a significant decrease in cell death by 62.69%. Under in vivo condition, after the 9th day of X-irradiation (equivalent to an accumulated dose of 14 Gy), the dorsal skin of 5 out of 6 NLC-ATX-untreated mice exhibited grade-1 skin damage, according to CTCAE v5.0, while treatment with NLC-ATX protected 6/6 mice from acute skin damage. Moreover, on the 28th day after the first X-irradiation, the histological images illustrated that NLC-ATX at an ATX concentration of 0.25 µg/mL exhibited good recovery of the skin, with barely any difference noted in the collagen fibers and sebaceous glands compared to normal skin. Conclusions: NLC-ATX shows potential for application in skin protection against adverse effects of ionizing rays during radiotherapy.