1*Jacob, FF Bioworks India Pvt Ltd. (Managing Director). Email: jacob.at@ffbioworks.com
2Jacob, FF Bioworks India Pvt Ltd. (Executive Director). Email: thomas.aj@ffbioworks.com
3Gopinathan, FF Bioworks India Pvt Ltd. (Research and Development). Email: gopinathan@ffbioworks.com
Purpose: Age-related macular degeneration and light-induced retinal injury are driven by photo-oxidative stress, lipofuscin (A2E) accumulation, mitochondrial dysfunction, and progressive photoreceptor loss, for which multi-targeted nutraceutical strategies are increasingly being explored. iXAN™ is a rationally designed, bioavailable lutein–zeaxanthin–curcuminoid formulation that targets multiple converging pathways of retinal degeneration, including photo-oxidative stress, lipofuscinogenesis, and mitochondrial dysfunction. The present study evaluated the cytoprotective, antioxidant, and retinal protective efficacy of iXAN™ using in vitro ARPE-19 cell models and an in vivo blue-light–induced retinal damage model, with emphasis on intracellular A2E modulation, bioavailability, and structural preservation.
Methods: Cytocompatibility, proliferative activity, UV-induced cytoprotection, and intracellular A2E levels were assessed in ARPE-19 cells using the MTT assay, fluorescence microplate analysis, and LC–MS/MS quantification. In vivo retinal injury was induced by blue-light exposure in rats followed by oral administration of iXAN™ at two dose levels. Serum antioxidant biomarkers (SOD, CAT, GPx, and total antioxidant capacity) were measured by ELISA. Plasma and retinal concentrations of lutein, zeaxanthin, and curcuminoids were quantified by LC–MS/MS. Retinal morphology was evaluated by hematoxylin and eosin staining.
Results: iXAN™ exhibited excellent cytocompatibility (>93% viability at 1000 µg/mL) and significantly enhanced ARPE-19 cell proliferation. UV exposure increased intracellular A2E and reduced cell viability, whereas iXAN™ restored cell survival and significantly suppressed A2E accumulation in a dose-dependent manner. In vivo, blue-light exposure depleted endogenous antioxidant defenses and retinal carotenoids, while treatment significantly restored SOD, CAT, GPx, and total antioxidant capacity. LC–MS/MS demonstrated enhanced systemic bioavailability and retinal deposition of lutein and zeaxanthin together with increased circulating curcuminoids. Histopathology revealed preservation of photoreceptor organization, maintenance of outer nuclear layer thickness, and attenuation of retinal degeneration in treated groups, with no treatment-related systemic toxicity or adverse effects on body weight observed.
Conclusions: iXAN™ confers multi-level protection against photo-oxidative retinal injury by restoring redox homeostasis, enhancing retinal carotenoid delivery, suppressing A2E accumulation, and preserving retinal architecture. These findings support its potential as a mechanistically targeted nutraceutical strategy for the prevention or adjunctive management of oxidative stress–mediated retinal disorders, including age-related macular degeneration.
Keywords: iXAN™, Age-related macular degeneration; lutein; zeaxanthin; curcuminoids; blue light; A2E; ARPE-19; antioxidant; retinal degeneration; LC–MS/MS.
How to cite this article: Jacob AT, Jacob TA, Gopinathan K. iXAN™ (Lutein, Zeaxanthin and Curcuminoids) Enhances Retinal Antioxidant Capacity and Macular Carotenoid Deposition to Attenuate Blue-Light–Induced Phototoxicity. Int J Drug Deliv Technol. 2026;16(15s): 89-107. DOI: 10.25258/ijddt.16.15s.11
Source of support: Nil.
Conflict of interest: None