Codelivery of synergistic antimicrobials with polyelectrolyte nanocomplexes to treat bacterial biofilms and lung infections

Bacterial biofilm infections, particularly those of Pseudomonas aeruginosa (PA), have high rates of antimicrobial tolerance and are commonly found in chronic wound and cystic fibrosis lung infections. Combination therapeu-tics that act synergistically can overcome antimicrobial tolerance; however, the delivery of multiple therapeutics at relevant dosages remains a challenge. We therefore developed a nanoscale drug carrier for antimicrobial co -delivery by combining approaches from polyelectrolyte nanocomplex (NC) formation and layer-by-layer electro-static self-assembly. This strategy led to NC drug carriers loaded with tobramycin antibiotics and antimicrobial silver nanoparticles (AgTob-NCs). AgTob-NCs displayed synergistic enhancements in antimicrobial activity against both planktonic and biofilm PA cultures, with positively charged NCs outperforming negatively charged formulations. NCs were evaluated in mouse models of lung infection, leading to reduced bacterial burden and improved survival outcomes. This approach therefore shows promise for nanoscale therapeutic co -delivery to treat recalcitrant bacterial infections.

Automated summary

Researchers have developed a nanoscale drug carrier that can deliver both antibiotics and antimicrobial silver nanoparticles to bacterial infections, showing synergistic antimicrobial effects against Pseudomonas aeruginosa. The carrier has also demonstrated positive outcomes in reducing bacterial burden and improving survival outcomes in a mouse model of lung infection.