Polyelectrolyte Nanocomplex Formation Combined with Electrostatic Self-Assembly Enables the Co-Delivery of Synergistic Antimicrobials to Treat Bacterial Biofilms

New approaches are needed to treat bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA). PA biofilms have high rates of antimicrobial resistance and are commonly found in chronic wound and cystic fibrosis lung infections. The use of combination therapeutics that act synergistically is a promising treatment strategy; however, the delivery of multiple therapeutics at relevant dosages is challenging in the clinic. We therefore developed a new nanoscale drug carrier by combining approaches from both polyelectrolyte nanocomplex (NC) formation and layer-by-layer electrostatic self-assembly. This strategy led to NC drug carriers functionalized with both tobramycin antibiotics and antimicrobial silver nanoparticles with high loading efficiencies. AgTob-NCs displayed synergistic enhancements in antimicrobial activity against planktonic and biofilm PA cultures, with positively charged NCs demonstrating complete biofilm eradication. Overall, this approach shows promise in the co-delivery of diverse classes of antimicrobials to overcome antimicrobial resistance and treat bacterial biofilm infections.