Unlocking the opportunities and challenges of green strategies for bioavailability enhancement of polyphenols
Polyphenols are among the most versatile secondary metabolites of plants, with significant therapeutic potential, including anti-inflammatory, cardioprotective, and antioxidant properties. However, limited bioavailability impedes their clinical application. These improvements have led to the use of synthetic stabilizers, toxic solvents, and high-energy inputs, raising concerns about the sustainability, scalability, and environmental impact of these techniques. The bioavailability of polyphenolic bioactives is an emerging area of interest, and green strategies have been developed to address it. Recently, a series of carrier-free delivery systems have also been developed, such as edible colloidal architectures, biopolymer nanoparticles, self-assembled nanostructures, and protein/polysaccharide conjugate nanocarriers, which can enhance solubility, stability, gastrointestinal performance, and release profiles. This review offers a critical analysis of approaches to improve polyphenol bioavailability, as well as recent developments in sustainable formulation design, physicochemical characterization, and translational considerations. This review critically examines the potential, limitations, and future research directions for developing safe, scalable, and environmentally friendly polyphenol delivery systems for therapeutic applications.