Fortified hyperbranched PEGylated chitosan-based nano-in-micro composites for treatment of multiple bacterial infections

[Display omitted] Bacterial resistance is a real threat to human health. One of the most common strategies used to overcome this problem is the combination therapy. This study proposes a new chitosan-based nano-in-microparticles (NIMs) antibacterial platform that can deliver multiple antibacterial therapeutics at the same time. Chitosan (CS) was PEGylated to overcome its limited water solubility. Then, the antibacterial activity of the resulting PEG-CS was fortified via conjugation with dendritic polyamidoamine hyperbranches (HB) as well as in-situ immobilization of silver nanoparticles (AgNPs) to be efficient against multiple bacterial strains. Montmorillonite nanoclay (MMT) was prepared and used to encapsulate ibuprofen (IBU) as anti-inflammatory drug to reduce any concomitant inflammatory response during bacterial infection. The successful synthesis of PEG-HBCS-AgNPs as well as IBU-MMT nanocomplex was confirmed using FTIR, 1H NMR, DSC, TGA and EDX. SEM micrographs showed a complete formation of NIM spherical particles with a size around 13 µm. Besides, the newly developed drugs-loaded CS-based NIM formulation showed a better widespread activity on the tested aerobic and anaerobic bacterial species, and it may represent, after further optimization, a promising approach for overcoming multiple-bacterial infection.