PVA-Stabilized and Coassembled Nano/Microparticles with High Payload of Dual Phytochemicals for Enhanced Antibacterial and Targeting Effect

The codelivery of multiple bioactive phytochemicals via nano/microparticles (NPs/MPs) represents a promising strategy for enhancing therapeutic efficacy. This study presents the development of novel poly(vinyl alcohol) (PVA)-stabilized hybrid particles designed for codelivery of palmatine hydrochloride (PAL) and glycyrrhizic acid (GL). Employing a straightforward coassembly method, we synthesized dual-drug particles achieving a high payload capacity of over 70%. The particles were characterized as uniform in size, within the nano/micron range, and exhibited a ζ-potential of −5.0 mV. The incorporation of PVA not only stabilized the particles but also refined the aggregation process, resulting in more uniform and finer particles approximately 1 μm in size. Spectral analysis and molecular dynamics simulations verified the presence of π–π stacking and hydrogen bonding between PAL and GL within the particles. In vitro antibacterial assays indicated that the hybrid particles had a lower minimum inhibitory concentration against Escherichia coli and Multidrug-Resistant Staphylococcus aureus than those of the pure drugs. In vivo biodistribution study in rats revealed that the PVA-stabilized particles revealed enhanced targeting to the liver, lung, and heart, demonstrating improved tissue selectivity compared with the solution group. In summary, the PVA-stabilized hybrid NPs/MPs represent an innovative and efficient platform for codelivery of multidrugs. These findings highlight the promise of coassembled particles for high loading, enhanced bioactivity, and targeted delivery, making them a strong candidate for future clinical applications.