Transporter-Modulating Anthocyanin Nanoparticles for Stabilized and Efficient Delivery

Abstract Anthocyanins (ACNs) exhibit poor stability and low bioavailability. These limitations restrict their functional activity and applications in food processing. In this study, we prepared ACNs-loaded nanoparticles by synthesizing thiolated hyaluronic acid and assembling THA/FA-zein@ACNs. The nanoparticles showed a uniform spherical shape with a size of 91.35 nm (PDI = 0.154 ± 0.023) and exhibited robust stability against processing and digestive stress. Caco-2 assays revealed their specific affinity for sodium-glucose cotransporter 1 (SGLT1), enabling active recognition, with SGLT1-mediated uptake being 2.3-fold higher than that mediated by glucose transporter 2 (GLUT2). The system showed reduced P-glycoprotein (P-gp)-mediated efflux, supporting a proposed “push–pull” transport model that maximizes absorption. Free ACNs exhibited a short half-life (0.528 ± 0.105) h, while THA/FA-zein@ACNs prolonged T1/2 to (1.611 ± 0.372) h. The nanoparticles also modulated gut microbiota composition and predicted microbial metabolic functions. This work provides a theoretical and practical foundation for the precise, high-efficiency delivery of functional bioactives.