Mild Oxidation of Plant Polyphenols Yields Modular Nanoparticle-Forming Materials with Drug Loading Capabilities

Plant polyphenols have attracted interest as green precursors for functional materials due to their unique chemical features. Here, an approach to formulate nanoparticles (NPs) from a hydrophobic (quercetin; QCT) and a hydrophilic (tannic acid; TA) polyphenol, by leveraging their propensity for oxidation, is presented. QCT and TA are partially oxidized to form oxQCT and oxTA, respectively. The materials are subsequently used to formulate NPs by nanoprecipitation alone or in the presence of hydrophilic and amphiphilic polymers. Characterization of oxQCT reveals a notable chemical change and increased thermal stability, with reduced antioxidant and anti-inflammatory activities compared to unmodified QCT. Conversely, oxTA shows an insignificant change in chemistry compared to pristine TA, yet it displays greater thermal stability, reduced antioxidant activity, and altered anti-inflammatory activity. Particle size and morphology of the formulated NPs are examined by dynamic light scattering (DLS), analytical ultracentrifugation (AUC), and transmission electron microscopy (TEM). The results indicate that co-formulating oxQCT and oxTA with different polymers impacts their particle size, polydispersity index, and morphology. Lastly, oxQCT and oxTA co-formulated with other polymers are capable of loading hydrophobic drugs such as amphotericin B and curcumin, forming sub-200 nm NPs with high loading efficiencies, which validates their use in drug delivery systems.