Antibiofilm Combinatory Strategy: Moxifloxacin-Loaded Nanosystems and Encapsulated <i>N</i>-Acetyl-L-Cysteine

Bacterial biofilms of Staphylococcus aureus, formed on implants, have a massive impact on the increasing number of antimicrobial resistance cases. The current treatment for biofilm-associated infections is based on the administration of antibiotics, failing to target the biofilm matrix. This work is focused on the development of multiple lipid nanoparticles (MLNs) encapsulating the antibiotic moxifloxacin (MOX). The nanoparticles were functionalized with d-amino acids to target the biofilm matrix. The produced formulations exhibited a mean hydrodynamic diameter below 300 nm, a low polydispersity index, and high encapsulation efficiency. The nanoparticles exhibited low cytotoxicity towards fibroblasts and low hemolytic activity. To target bacterial cells and the biofilm matrix, MOX-loaded MLNs were combined with a nanosystem encapsulating a matrix-disruptive agent: N-acetyl-L-cysteine (NAC). The nanosystems alone showed a significant reduction of both S. aureus biofilm viability and biomass, using the microtiter plate biofilm model. Further, biofilms grown inside polyurethane catheters were used to assess the effect of combining MOX-loaded and NAC-loaded nanosystems on biofilm viability. An increased antibiofilm efficacy was observed when combining the functionalized MOX-loaded MLNs and NAC-loaded nanosystems. Thus, nanosystems as carriers of bactericidal and matrix-disruptive agents are a promising combinatory strategy towards the eradication of S. aureus biofilms