The global spread of multi-drug-resistant (MDR) bacteria is rapidly increasing due to antibiotic overuse, posing a major public health threat and causing millions of deaths annually. The present study explored the potential of nanocarriers for delivering novel and alternative antibacterial agents using nanotechnology-based approaches to address the challenge of MDR bacteria. The purpose was to enhance the solubility, stability, and targeted delivery of berberine (BER) and its synthetic derivative NR16 using Styrene-co-Maleic Acid (SMA) nanoparticles. Characterization of the nanoparticles, including dynamic light scattering (DLS) analysis, TEM, and UV/Vis absorption spectroscopy, confirmed their suitability and high stability for passive drug delivery. Antibacterial and antifungal activities were evaluated against a panel of pathogens, revealing significant inhibitory effects on Gram-positive strains; particularly BER, SMA-BER, and NR16 were active against MRSA, MSSA, VR, and VS E. faecalis, and S. epidermidis. Additionally, SMA-BER and SMA-NR16 showed promising activity against biofilm formation of S. epidermidis; while the two free drugs contributed to S. epidermidis biofilm disruption activity. Hemolysis tests and in vitro studies on human embryonic kidney cells (HEK-293) confirmed the safety profiles of the nanoparticles and free drugs. Overall, this research highlighted the potential of nanotechnology in developing effective antibacterial agents with reduced toxicity, addressing the growing threat of MDR bacterial infections.
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