Enhanced Activity and Sustained Release of Protocatechuic Acid, a Natural Antibacterial Agent, from Hybrid Nanoformulations with Zinc Oxide Nanoparticles

Hybrid nanostructures can be developed with inorganic nanoparticles (NPs) such as zinc oxide (ZnO) and natural antibacterials. ZnO NPs can also exert antibacterial effects, and we used them here to examine their dual action in combination with a natural antibacterial agent, protocatechuic acid (PCA). To produce hybrid nanoformulations, we functionalized ZnO NPs with four types of silane organic molecules and successfully linked them to PCA. Physicochemical assessment confirmed PCA content up to ~18% in hybrid nanoformulations, with a PCA entrapment efficiency of ~72%, indicating successful connection. We then investigated the in vitro release kinetics and antibacterial effects of the hybrid against Staphylococcus aureus. PCA release from hybrid nanoformulations varied with silane surface modification. Within 98 h, only 8% of the total encapsulated PCA was released, suggesting sustained long-term release. We used nanoformulation solutions collected at days 3, 5, and 7 by disc diffusion or log reduction to evaluate their antibacterial effect against S. aureus. The hybrid nanoformulation showed efficient antibacterial and bactericidal effects that also depended on the surface modification and at a lower minimum inhibition concentration compared with the separate components. A hybrid nanoformulation of the PCA prodrug and ZnO NPs offers effective sustained-release inhibition of S. aureus growth.