Co-Delivery of Synergistic Antimicrobials with Polyelectrolyte Nanocomplexes to Treat Bacterial Biofilms and Lung Infections

Abstract

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.

Formulation and characterization of Benzydamine loaded casein/chitosan nanocomplexes

“…Polyelectrolyte complexes at the nanoscale formulated from biocompatible polymers are currently being widely investigated for their medical applications as drug delivery systems as well as for diagnostic, medical imaging and tissue engineering purposes [5]. These systems offer many advantages over conventional delivery systems as they focus on efficacy of the active compound by improving its bioavailability and targeted delivery [6] and safety, extending the molecule half-life in the target tissue [7] and enhancing its stability against chemical and/or enzymatic degradation [8]. The main properties of the nanostructures that influence their selection as drug-delivery systems are the size and morphology of the particles, the surface charge, drug loading and the desired release profile [9].…”