Abstract
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.