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The present work aims to synthesize the rifaximin loaded chitosan-alginate core-shell nanoparticles (Rif@CS/Alg-NPs) for antibacterial applications. The core-shell nanoparticles (Rif@CS/Alg-NPs) were characterized by Fourier Transform Infrared (FT-IR) spectroscopy, Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), X-rays diffraction (XRD) and zeta analyzer. The antibacterial activities of Rif@CS/Alg-NPs were investigated against three species of bacteria namely Escherichia coli (E. coli), Pseudomonas aerugi