Chitosan-graft-poly(lactide) nanocarriers: An efficient antioxidant delivery system for combating oxidative stress

Oxidative stress is a key factor in various diseases, and thus exogenous antioxidants offer effective therapeutic potential. While astaxanthin (ATX) is a potent natural antioxidant, its poor water solubility, bioavailability, and stability hinder its application. This study aimed to develop an amphiphilic chitosan-graft-poly(lactide) (CS-g-PLA) copolymer utilizing a new strategy by ring-opening polymerization of D, l-lactide via organosoluble CS/sodium dodecyl sulfate complex. Subsequently, CS-g-PLA micelles were prepared for efficient encapsulation and delivery of ATX. CS-g-PLA copolymers were characterized by FT-IR and ¹H NMR. Transmission electron microscopy and dynamic light scattering revealed micellar morphology and size distribution. The antioxidant activity of CS-g-PLA/ATX was assessed using the DPPH assay, demonstrating significant improvement compared to free ATX. Furthermore, the cytotoxicity of micellar ATX was evaluated on H₂O₂-treated bone marrow mesenchymal stem cells (BMSCs) using MTT assay. Annexin V staining and mitochondrial membrane potential (∆Ψm) analysis revealed reduced apoptosis and enhanced protection by ATX-loaded micelles compared to free ATX. These findings suggest CS-g-PLA micelles as promising nanocarriers for ATX delivery, putatively enhancing its antioxidant potential and protecting stem cells in oxidative stress environments. This approach could hold significant implications for stem cell therapy in diseases associated with oxidative stress.