Self‐Assembled Synergistic Nanoparticles from Carrier‐Free Berberine and Ferulic Acid for Improved Antibacterial Activity

Abstract With the widespread overuse of antibiotics, Staphylococcus aureus has developed multiple resistances to a variety of first‐line antibiotics; therefore, it is imperative to explore novel antimicrobial strategies to solve the problem of resistance. Traditional Chinese medicines (TCM) are considered sources of chemicals with potential healing properties. In this study, berberine (BBR) and ferulic acid (FA) were used as raw materials to prepare nanoparticles with enhanced antibacterial activity by self‐assembly technology. The study revealed that the self‐assembly process involves non‐covalent interactions. Minimum inhibitory concentration (MIC) of the FA‐BBR NPs was 0.1 µmol/mL, and the antibacterial rate of FA‐BBR NPs with a concentration of 0.2 µmol/mL against S. aureus was 94.56 ± 0.57%, which was significantly higher than monomers. The Bradford protein concentration assay was used to analyze the leakage of cellular contents. Scanning electron microscopy (SEM) and the fluorescent probe DiSC 3 (5) revealed that the nanoparticles can affect the integrity and permeability of bacterial biofilm, which is a key factor contributing to their superior antibacterial activity.