Nanotechnology and machine learning synergies for improving the bioavailability and functional efficacy of dietary polyphenols

Dietary polyphenols exhibit diverse bioactivities, but their clinical application is limited by poor bioavailability due to low solubility, rapid metabolism, and restricted absorption. This review systematically summarizes recent advances in nanocarrier-based strategies for improving dietary polyphenol delivery. Four representative nanocarrier types are analyzed, including liposomes, solid lipid nanoparticles, nanosuspensions, and polymeric micelles. We discuss how their physicochemical properties and interfacial interactions enhance solubility, stability, and targeted delivery, while also highlighting limitations such as potential toxicity, limited loading capacity, and formulation complexity. A key focus of this review is the integration of machine learning (ML) into nanocarrier design to optimize performance. Supervised models such as support vector machines, random forests, and XGBoost achieve high predictive accuracy for encapsulation efficiency, release kinetics, and biodistribution. ML further enables high-throughput screening, toxicity prediction, and iterative refinement of formulations, improving the efficacy and safety of dietary polyphenol delivery. ML-driven integration of multi-omics data provides mechanistic insights into interactions among nanocarriers, polyphenols, and biological systems, supporting biomarker discovery and precision delivery. Additionally, we present a stepwise workflow that integrates nanotechnology and ML to guide the rational development of dietary polyphenol formulations. Finally, we discuss current challenges, including data heterogeneity, model interpretability, and regulatory considerations, and outline future directions to advance ML-driven nanocarrier strategies for efficient dietary polyphenol delivery. In conclusion, this review provides a comprehensive framework and highlights the unique contribution of integrating nanotechnology and ML for designing next-generation functional foods and precision nutrition.