Bridging the Bioavailability Barriers of Apigenin via Modern Engineering Strategies: A Comprehensive and Critical Review

Apigenin (AP) is a natural flavonoid with diverse bioactivities, attracting considerable attention in clinical therapy, functional foods, and dietary supplements. However, its strong hydrophobicity, poor intestinal permeability, and rapid in vivo elimination result in negligible bioavailability, severely hindering its clinical translation. To address these challenges, this review provides a comprehensive analysis of the pharmacokinetic (absorption, distribution, metabolism, and excretion, ADME) characteristics of apigenin, identifying the key biological barriers. On this basis, three interconnected, cutting-edge engineering strategies are systematically evaluated: chemical modification to optimize molecular structure for improved solubility, bioactivity, and metabolic stability; novel delivery systems to protect apigenin from degradation, facilitate its sustained release and absorption, and enhance targeted therapeutic efficacy; synergistic combination therapy to enhance the clinical efficacy of multiple components while reducing toxic side effects. Future research directions are highlighted, focusing on microenvironment-responsive smart platforms, AI-assisted predictive models, and an interdisciplinary framework integrating pharmaceutical science and nutrition. These convergent advances are expected to break through the bioavailability bottleneck of apigenin and establish a new paradigm for improving the translational potential of bioactive flavonoids.