This study involves the investigation of astaxanthin-loaded nanoparticles under oxidative stress conditions in two human cell lines: HUVEC (human umbilical vein endothelial cells) for assessing oxidative stress, and Caco-2 (human colorectal adenocarc. Homo Sapiens

Oxidative stress is a pathological condition characterized by an imbalance between excessiveROS production and insufficient antioxidant defenses, contributing to the onset of variousdiseases, including cancer, cardiovascular disorders, and neurodegenerative diseases. This studyexplores the potential of NLC loaded with astaxanthin, a potent carotenoid antioxidant, toenhance bioavailability and therapeutic efficacy in mitigating oxidative stress-related damage.The primary objectives of this investigation were threefold: (1) to design and optimize theencapsulation of astaxanthin within the NLC delivery system, (2) to determine the optimalconcentration of NLC-A that effectively reduces oxidative stress in HUVECs and inducesapoptosis in Caco-2 cells, and (3) to elucidate the molecular mechanisms underlying thesebiological responses by analyzing key gene expressions related to antioxidant defenses andapoptotic signaling pathways.In vitro assessments utilized AMA and AAPH as oxidative agents. Results demonstrated thatNLC-A effectively reduced ROS production by up to 52%, indicating substantial protectiveeffects on HUVECs. Mechanistic studies revealed significant upregulation of antioxidant genes,including Nrf2, NQO1, and HO-1, which highlighted the ability of NLC-A to activate cellulardefense mechanisms. Furthermore, treatment with NLC-A in Caco-2 cells resulted in a markedinduction of apoptosis, evidenced by the downregulation of the anti-apoptotic protein Bcl-2 andactivation of Caspase-3, elucidating a potential pathway for cancer cell elimination.These findings illustrate the dual action of astaxanthin-loaded NLCs in providing cytoprotectionagainst oxidative stress while promoting apoptosis in colon cancer cells. Consequently, NLC-Apresents a promising therapeutic approach for addressing oxidative stress-related disorders andcolorectal cancer. Future research directions will focus on understanding the detailed molecularmechanisms of action and evaluating the efficacy of NLC-A in preclinical and clinical settings.