Nanocarrier Systems for Plant-Derived Bioactives: Design, Biosafety, and Translational Challenges.

Plant-derived bioactives offer diverse pharmacological activities, but their development is often limited by poor aqueous solubility, instability, rapid metabolism, and low tissue exposure. This review examines delivery platforms used to address these constraints, including liposomes, solid lipid nanoparticles, nanostructured lipid carriers, phytosomes, niosomes, polymeric and protein-based carriers, extracellular vesicles, and self-assembled polyphenol systems. The platforms are compared according to payload compatibility, loading and release behavior, biological barriers, manufacturing requirements, and formulation-specific safety risks. Though carriers of natural origin offer a sustainable and often less toxic alternative, their ability to induce immunogenicity, organ accumulation, and repeated-dose toxicity require product-specific assessment. The review also discusses sustainable extraction and formulation, emphasizing that green performance depends on the entire process rather than on the feedstock alone. Preclinical studies frequently report improved stability, exposure, or therapeutic activity, whereas human evidence remains limited and is concentrated in early-phase studies of curcumin and silybin formulations and a small number of plant-derived extracellular-vesicle preparations. Translation will require standardized characterization, defined critical quality attributes, scalable Good Manufacturing Practice-compliant production, batch consistency, comparative pharmacokinetic and toxicological studies, and appropriately powered clinical trials. These considerations support rational carrier selection based on the physicochemical properties of the bioactive, intended route and target, release requirements, and strength of the available evidence.