Phlorotannins from Phaeophyceae: Structural Diversity, Multi-Target Bioactivity, Pharmacokinetic Barriers, and Nanodelivery System Innovation.

Phlorotannins, a unique group of polyphenolic compounds derived exclusively from brown macroalgae (Phaeophyceae), have gained substantial scientific and industrial interest due to their structural diversity and multifaceted bioactivities. These marine metabolites, composed of phloroglucinol units linked through various C-C and C-O-C bonds, exhibit broad-spectrum antioxidant, anti-inflammatory, antimicrobial, antidiabetic, anticancer, and neuroprotective effects. Despite their promising in vitro efficacy, large-scale application remains hindered by three critical translational barriers: (i) extreme natural variability in phlorotannin content driven by ecological and seasonal factors, complicating raw material standardization; (ii) physicochemical instability and poor aqueous solubility resulting in limited oral bioavailability; and (iii) insufficient development of advanced delivery systems to ensure controlled release and targeted bioactivity. This comprehensive review integrates ecological, biochemical, and technological perspectives to establish a unified framework for translating phlorotannin research toward clinical and commercial realization. It systematically examines biosynthetic regulation, structural classification, extraction and purification methods, bioactivity mechanisms, pharmacokinetic barriers, and toxicological safety considerations. The review concludes by highlighting future research priorities essential for achieving industrial scalability, formulation reproducibility, and regulatory acceptance in marine bioactive development.