PVA-Stabilized\nand Coassembled Nano/Microparticles\nwith High Payload of Dual Phytochemicals for Enhanced Antibacterial\nand Targeting Effect

The codelivery of multiple bioactive phytochemicals via\nnano/microparticles\n(NPs/MPs) represents a promising strategy for enhancing therapeutic\nefficacy. This study presents the development of novel poly(vinyl\nalcohol) (PVA)-stabilized hybrid particles designed for codelivery\nof palmatine hydrochloride (PAL) and glycyrrhizic acid (GL). Employing\na straightforward coassembly method, we synthesized dual-drug particles\nachieving a high payload capacity of over 70%. The particles were\ncharacterized as uniform in size, within the nano/micron range, and\nexhibited a ζ-potential of −5.0 mV. The incorporation\nof PVA not only stabilized the particles but also refined the aggregation\nprocess, resulting in more uniform and finer particles approximately\n1 μm in size. Spectral analysis and molecular dynamics simulations\nverified the presence of π–π stacking and hydrogen\nbonding between PAL and GL within the particles. In vitro antibacterial\nassays indicated that the hybrid particles had a lower minimum inhibitory\nconcentration against Escherichia coli and Multidrug-Resistant Staphylococcus aureus than those of the pure drugs. <i>In vivo</i> biodistribution\nstudy in rats revealed that the PVA-stabilized particles revealed\nenhanced targeting to the liver, lung, and heart, demonstrating improved\ntissue selectivity compared with the solution group. In summary, the\nPVA-stabilized hybrid NPs/MPs represent an innovative and efficient\nplatform for codelivery of multidrugs. These findings highlight the\npromise of coassembled particles for high loading, enhanced bioactivity,\nand targeted delivery, making them a strong candidate for future clinical\napplications.