Orally administered dual-targeted astaxanthin nanoparticles as novel dietary supplements for alleviating hepatocyte oxidative stress.

The enhancement of bioavailability of food bioactive compounds as dietary supplements can be achieved through the development of targeted delivery systems. This study aimed to develop a novel dual-targeted delivery system for hepatocytes and mitochondria using phacoemulsification self-assembly. The delivery systems were engineered by modifying whey protein isolate (WPI) with galactose oligosaccharide (GOS) and triphenylphosphonium (TPP) to improve AXT transport to the liver and promote hepatic well-being. The dual-targeted nanoparticles (AXT@TPP-WPI-GOS) significantly reduced reactive oxygen species in in vitro experiments, thereby slowing down apoptosis. The AXT@TPP-WPI-GOS exhibited a prominent mitochondrial targeting capacity with a Pearson correlation coefficient of 0.76 at 4 h. In vivo pharmacokinetic experiments revealed that AXT@TPP-WPI-GOS could enhance AXT utilization by 28.18 ± 11.69%. Fluorescence imaging in mice demonstrated significantly higher levels of AXT@TPP-WPI-GOS accumulation in the liver compared to that of free AXT. Therefore, these nanoparticles hold promising applications in nutrient fortification, improving the bioavailability of AXT and supporting hepatic well-being.