Diminishing biofilm resistance to antimicrobial nanomaterials through electrolyte screening of electrostatic interactions

The extracellular polymer substances (EPS) generated by biofilms confers resistance to antimicrobial agents through electrostatic and steric interactions that hinder molecular diffusion. This resistance mechanism is particularly evident for antibacterial nanomaterials, which inherently diffuse more slowly compared to small organic antibacterial agents. The aim of this study was to determine if a biofilm's resistance to antibacterial nanomaterial diffusion could be diminished using electrolytes to screen the EPS's electrostatic interactions. Anionic (+) alpha-tocopherol phosphate (alpha-TP) liposomes were used as the antimicrobial nanomaterials in the study. They self-assembled into 700 nm sized structures with a zeta potential of -20 mV that were capable of killing oral bacteria (S. oralis growth inhibition time of 3.34 +/- 0.52 h). In a phosphate (-ve) buffer the -ve alpha-TP liposomes did not penetrate multispecies oral biofilms, but in a Tris (hydroxymethyl)aminomethane (+ ve) buffer they did (depth - 12.4 +/- 3.6 mu m). The Tris did not modify the surface charge of the alpha-TP nanomaterials, rather it facilitated the alpha-TP-biofilm interactions through electrolyte screening (Langmuir modelled surface pressure increase of 2.7 +/- 1.8 mN/m). This data indicated that EPS resistance was mediated through charge repulsion and that this effect could be diminished through the co-administration of cationic electrolytes.