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

Abstract

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.

Antibacterial hydrogel therapy for eradication of wound associated polymicrobial biofilms

“…The increased susceptibility of P. aeruginosa and S. aureus biofilms accounts for potent antibiofilm capacity of ultrasmall AgNPs that can accumulate within biofilm structure facilitating structural damage and enhanced bacterial penetration. 14,21 We have previously shown that the small sized AgNPs can overcome single species biofilm structural barrier with favourable uptake resulting in biofilm disintegration, against both Gram-negative and -positive bacteria using clinically relevant in vitro and preclinical animal infection wound models where their application was safe and no adverse effects were observed. 14,21 Nanoparticle's size dependent antibacterial effect of silver has also been studied using mesoporous silica nanoparticles, 22 biofilm responsive nanoantibiotic containing small sized AgNPs 23 and surface coated ultrasmall AgNPs to boost antibacterial efficacy.…”

“…14,21 We have previously shown that the small sized AgNPs can overcome single species biofilm structural barrier with favourable uptake resulting in biofilm disintegration, against both Gram-negative and -positive bacteria using clinically relevant in vitro and preclinical animal infection wound models where their application was safe and no adverse effects were observed. 14,21 Nanoparticle's size dependent antibacterial effect of silver has also been studied using mesoporous silica nanoparticles, 22 biofilm responsive nanoantibiotic containing small sized AgNPs 23 and surface coated ultrasmall AgNPs to boost antibacterial efficacy. 24 It is noteworthy that ultrasmall size AgNPs are highly susceptible to fast oxidation and dissolution, facilitating fast leaching of silver ions and short antibacterial duration with associated potential toxicity.…”