Biocompatible Polycationic Silver Nanocluster-Impregnated PLGA Nanocomposites with Potent Antimicrobial Activity

Ultrasmall cationic silver nanoparticles (AgNPs) have recently emerged as highly potent antimicrobial agents for the treatment of multidrug-resistant bacteria and their biofilms. However, the clinical application of these cationic AgNPs is hampered by their poor stability and high reactivity in solution, leading to uncontrolled release of toxic silver ions. An ideal platform featuring broad-spectrum antibacterial activity and high biocompatibility that prevents overexposure to silver ions, is therefore highly desirable. Herein, we explored a biocompatible and biodegradable polymer, poly(lactic-co-glycolic) acid (PLGA) as an effective carrier for the recently discovered polycationic silver nanoclusters (pAgNCs). These pAgNCs impregnated PLGA nanocomposites (pAgNCs@PLGA) were developed by water-in-oil-in-water (W₁/O/W₂) emulsion method and characterized by various analytical techniques. Our experimental results reveal that pAgNCs@PLGA had spherical morphology with an average diameter of ∼188 nm and consists of multiple ultrasmall (∼2 nm) pAgNCs at the polymeric core. The minimum inhibitory concentration of pAgNCs for Staphylococcus aureus and Pseudomonas aeruginosa were found to be 6.9 μg/mL. After impregnation within PLGA, the antimicrobial efficacy of our pAgNCs against Staphylococcus aureus and Pseudomonas aeruginosa remained consistent, while the nanocomposites were biocompatible at the minimum inhibitory concentration (MIC) against both bacteria. The pAgNCs@PLGA nanocomposite developed in this work may present a path forward to bring these highly potent pAgNCs into medical practice.