Layer-By-Layer Decorated Nanoparticles with Tunable Antibacterial and Antibiofilm Properties against Both Gram-Positive and Gram-Negative Bacteria.

Abstract

Bacteria-mediated diseases are a global healthcare concern due to the development and spread of antibiotic-resistant strains. Cationic compounds are considered membrane active biocidal agents having a great potential to control bacterial infections, while limiting the emergence of drug resistance. Herein, the versatile and simple layer-by-layer (LbL) technique is used to coat alternating multilayers of an antibacterial aminocellulose conjugate and the biocompatible hyaluronic acid on biocompatible polymer nanoparticles (NPs), taking advantage of the nanosize of these otherwise biologically inert templates. Stable polyelectrolyte-decorated particles with an average size of 50 nm and ζ potential of +40.6 mV were developed after five LbL assembly cycles. The antibacterial activity of these NPs against the Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli increased significantly when the polycationic aminocellulose was in the outermost layer. The large number of amino groups available on the particle surface, together with the nanosize of the multilayer conjugates, improved their interaction with bacterial membrane phospholipids, leading to membrane disruption, as confirmed by a Langmuir monolayer model, and the 10 logs reduction for both bacteria. The biopolymer decorated NPs were also able to inhibit the biofilm formation of S. aureus and E. coli by 94 and 40%, respectively, without affecting human cell viability. The use of LbL-coated NPs appears to be a promising antibiotic-free alternative for controlling bacterial infections using a low amount of antimicrobial agent.