Astaxanthin-loaded alginate-chitosan gel beads activate Nrf2 and pro-apoptotic signalling pathways against oxidative stress

Abstract

Oxidative stress (OS) plays a crucial role in disease development. Astaxanthin (ATX), a valuable natural compound, may reduce OS and serve as a treatment for diseases like neurodegenerative disorders and cancer. Nuclear factor-erythroid 2-related factor 2 (Nrf2) regulates antioxidant enzymes and OS management. We evaluated ATX’s antioxidant activity via Alg-CS/ATX gel beads in vitro. ATX-encapsulated alginate-chitosan (Alg-CS/ATX) gel beads were synthesized and structurally/morphologically characterized by SEM, FT-IR, and XRD. Their biological effects were examined in human umbilical vein endothelial cells (HUVECs) treated with H₂O₂ through MTT assay, Annexin V/PI, cell cycle studies, and western blotting. Alg-CS effectively carried ATX, with high capacity and reduced pore size. Alg-CS/ATX displayed an 84% encapsulation efficiency, maintaining stability for 30 days. In vitro studies showed a 1.4-fold faster release at pH 5.4 than at neutral pH, improving ATX’s therapeutic potential. HUVECs treated with Alg-CS/ATX showed enhanced viability via increased Nrf2 expression. Alg-CS gel beads exhibit significant potential as a biocompatible vehicle for delivering ATX to combat OS with considerable opportunity for clinical applications.

Keywords:

• Alginate bead
• astaxanthin
• biodegradable polymer
• chitosan
• encapsulation
• oxidative stress

Acknowledgements

We would like to extend our gratitude to the Research Center for Pharmaceutical Nanotechnology (RCPN) at Tabriz University of Medical Sciences and University of Tabriz for the technical support. We would like to thank Dr. Marcia M. Gowing (University of California, USA), and Dr. Yuri Okolodkov (University Veracruzana, Mexico) and Dr. Jaber Dehghani (University of Tabriz, Iran) for their comments during the project.

Author contributions

All authors conceived and planned the project. HG and EDA performed the experiments. HG, MF, AM, JB, and YO analysed and reviewed data. HG and MF drafted the manuscript. AM, JB, HO, and YO edited the manuscript. All authors contributed to discussing the results.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This project is part of a Ph.D. thesis financially supported by the Research Centre for Pharmaceutical Nanotechnology (RCPN) at the Tabriz University of Medical Sciences (#RCPN 68244).