The emergence of antibiotic resistance has raised the need for engineering novel highly effective antibacterials with reduced toxicity and lower selection for resistant bacterial strains. Targeted drug delivery nanosystems hold significant promise to improve the efficacy of the existing antimicrobials and advance the treatment of severe bacterial infections, lowering the risk of resistance occurrence. In this work, we aimed to develop antibacterial nanocapsules (NCs) decorated with targeting ligands for driving with high specificity the therapeutic cargo to the target S. aureus pathogen. Oregano oil loaded NCs with size of 195 nm, low polydispersity index and broad spectrum antibacterial activity were produced via a self-assembling nanoencapsulation technology based on biocompatible natural polymers. Layer-by-layer assembly of hyaluronic acid and aminocellulose biopolymers was further performed to introduce surface anchoring motifs for covalent grafting of specific for S. aureus antibody, as well as to improve the stability, biocompatibility and release profiles of the designed antibacterial oil-loaded NCs. The grafting of the selected antibody increased the NCs bactericidal efficacy against S. aureus by 2 logs. Furthermore, the targeting selectivity of the bactericidal NCs was confirmed via incubation with a mixed inoculum containing Gram-negative P. aeruginosa and E.coli. The formulated S. aureus-targeting NCs selectively reduced the growth of S. aureus, but did not affect the normal growth of non-targeted bacteria. Coating the antibacterial NCs with biocompatible polymers and subsequent grafting of the pathogen specific antibody through the available amino groups increased the compatibility of the oil-loaded NCs to human cells and reduced their side effects.

Engineering of safe nanocapsules for targeted antibacterial applications

2019 Spring National Meeting

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