Chitosan-caseinate-dextran ternary complex nanoparticles for potential oral delivery of astaxanthin with significantly improved bioactivity

Astaxanthin (ASTX) has been reported as a potential therapeutic agent for hepatic fibrosis treatment. However, its therapeutic effect is limited due to low bioavailability and poor aqueous solubility. In this study, biopolymer-based nanoparticles were fabricated using stearic acid-chitosan conjugate (SA-CS) and sodium caseinate (NaCas) via ionic gelation. Its nanostructure was cross-linked using oxidized dextran (Odex) via Schiff base reaction. Concentration of cross-linker, cross-linking temperature and time were systematically optimized by response surface methodology (RSM) to achieve superior particulate properties and colloidal stability. The optimized nanoparticles exhibited a diameter of 120 nm with homogeneous size distribution. A good ASTX encapsulation capacity with up to 6% loading ratio and high encapsulation efficiency was obtained. The final ASTX concentration in nanoparticles was 140 μM. The aqueous dispersibility of encapsulated ASTX was greatly improved, which was confirmed by significantly increased ABTS radical scavenging capacity. Compared to the anti-fibrogenic effect of free ASTX in LX-2 cells, the encapsulated ASTX demonstrated dramatically enhanced cellular bioactivity, as evidenced by significantly lower TGFβ1-induced fibrogenic gene (ACTA2 and COL1A1) expression level, as well as α-SMA and COL1A1 protein levels. This study suggests that the as-prepared biopolymer nanoparticles hold promising features as an oral delivery vehicle for lipophilic bioactives.