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

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. Graphical A self-assembled carrier-free nano drug delivery system composed of ferulic acid and berberine was developed using a one-step self-assembly approach. FA-BBR NPs were found to significantly improve the solubility and antibacterial activity of the individual traditional Chinese medicine compounds. The two components primarily interact through noncovalent forces, including hydrogen bonding, ᴨ-ᴨ stacking, and electrostatic interactions. Further investigation revealed that FA-BBR NPs exerted enhanced antibacterial effects by compromising the integrity and permeability of bacterial cell membranes.