Polyphenolic phytosomes for targeted drug delivery

Currently, the attention of researchers is attracted by natural polyphenolic compounds, including flavonoids, which exhibit pronounced antioxidant, anti-inflammatory, and antitumor properties. More than 8500 phenolic compounds have been isolated and characterized from plant sources. Despite their therapeutic potential, clinical translation is limited by low water solubility, poor membrane permeability, and extensive first-pass metabolism, resulting in suboptimal bioavailability. This review provides a comprehensive analysis of phytosome technology, including the mechanism of complex formation, structural advantages compared to traditional nanocarriers, and its impact on pharmacokinetics and bioefficacy. Polyphenolic compounds, such as silybin, curcumin, quercetin, epigallocatechin gallate (EGCG), and grape seed proanthocyanidins, have been successfully formulated into phytosomes, resulting in a significant enhancement of oral bioavailability and therapeutic efficacy in both preclinical and clinical studies. It also highlights evidence from clinical trials involving phytosomal formulations in various disease contexts, including cancer, liver and metabolic disorders, neurodegeneration, and COVID-19. The safety profile of phytosomes is favorable, with most formulations well-tolerated even under long-term use. Current limitations, including formulation instability, lack of regulatory clarity, and challenges in industrial scale-up, are discussed alongside future directions in targeted delivery and combination therapies. Phytosomes represent a clinically viable platform that bridges natural product pharmacology with modern drug delivery technologies, offering a scalable and biocompatible strategy for improving the clinical impact of polyphenols.