Construction of chitosan hydrochloride‐carboxymethyl chitosan nanoparticles using anti‐solvent method for the co‐delivery of puerarin and resveratrol

Abstract The applications of resveratrol (RES) and puerarin (PUE) with notable physiological functions are greatly limited in functional food and pharmaceutical industries due to their poor water solubility and chemical instability. Accordingly, co‐loading of RES and PUE into chitosan‐based nanoparticles (NPs) is performed here by an anti‐solvent method to improve their bioavailability. The fabricated NPs at 8:1 mass ratio of carboxymethyl chitosan (CMC) to chitosan hydrochloride (CHC) with the particle size of 375.1 nm and zeta potential of +36.5 mV showed encouraging encapsulation efficiency and loading capacity at 85.2% (RES), 89.5% (PUE), and 15.5%. The microstructure of core–shell CMC–CHC was confirmed through dynamic light scattering and transmission electron microscopy. Molecular docking and storage stability indicating the more beneficial encapsulation of chitosan derivatives to PUE in comparison to RES. Cellular antioxidant activity experiments showed that the bioactivities of PUE/RES after loading with 20 and 40 mg·mL −1 were improved by 13.2% and 18.5%, respectively, with respect to free ones. Therefore, RES/PUE‐loaded CHC–CMC NPs were successfully prepared in this study, thus significantly improving the RES and PUE bioavailability and promoting their applications in functional food and pharmaceutical industries.