Fabrication, Characterization, Interactions, and Controlled Release of Quercetin by Surface-Functionalized Nanoparticle-Protein Corona

This study investigated the interactions between surface-modified starch nanoparticles and digestive enzymes (pepsin and trypsin), with emphasis on enzyme activity modulation, protein corona formation, and quercetin release kinetics. Three quercetin-loaded nanoparticle formulations were prepared: unmodified starch nanoparticles (QSNP), amine-functionalized (QNH 2 ), and carboxyl-functionalized (QCOOH). The protein corona formation on the starch nanoparticles was found to be strongly influenced by their surface properties, as shown by quartz crystal microbalance, atomic force microscopy, circular dichroism, and thermal analyses. QNH 2 formed a thick and soft cationic protein corona, which greatly reduced enzyme activities (especially trypsin), whereas the corona effect was minimal for QSNP. The quercetin release of QNH 2 (36.2%) was lower than that of QSNP (53.6%), which was attributed to corona thickness/charge differences. Thermal analysis confirmed that the nanoparticles remained stable after adsorption of proteins, with QNH 2 being the most thermally stable, followed by QSNP and QCOOH. These findings suggest that modulating the surface charge and functional groups of nanoparticles can alter their interactions with digestive enzymes, which may be used to control the release of encapsulated bioactive compounds. These insights are critical for the design of effective oral delivery systems for nutraceutical and pharmaceuticals.