Lipid-Coated Hybrid Nanoparticles for Enhanced Bacterial Biofilm Penetration and Antibiofilm Efficacy

Abstract Background: The biofilm way of life is a common strategy for bacteria to adapt and gain tolerance towards antibiotic treatments. Up to 80% of all infections are biofilm-mediated and they are often challenging to treat as the underlying bacterial cells can become 100 – 1000-fold more tolerant towards antibiotics. Antibiotic-loaded nanoparticles have gained traction as a potential drug delivery system to treat biofilm infections. Specifically, lipid-coated hybrid nanoparticles (LCHNPs) were investigated on their capability to deliver antibiotics into biofilms. In this study, LCHNPs composed of a poly(lactic-co-glycolic acid) (PLGA) core and dioleoyl-3-trimethylammonium propane (DOTAP) lipid shell were developed and loaded with vancomycin (Van). In vitro antibacterial and antibiofilm tests were performed to evaluate the antimicrobial efficacy of the LCHNPs. Results: LCHNPs were successfully fabricated with high vancomycin encapsulation efficiency of 48.66% and loading efficiency of 72.99 µg/mg. DOTAP was determined to be successfully coated on the PLGA core by measuring the ζ-potential of the nanoparticles. LCHNPs had a positive ζ-potential of +36.13 mV which contrasted significantly from the ζ-potential of -36.83 mV of bare PLGA nanoparticles (PLGANPs). LCHNPs exhibited enhanced antibacterial effects against planktonic Staphylococcus aureus USA300 cells, with at least 6-fold reduction in minimum inhibitory concentration when compared against Free-Van and Van-PLGANPs. When used to treat USA300 biofilms, Van-LCHNPs eradicated up to 99.99% of the underlying biofilm cells, an effect which was not observed for Free-Van and Van-PLGANPs. Finally, we showed that by possessing a robust DOTAP shell, LCHNPs were able to penetrate deeply into the biofilms. Conclusion: LCHNPs were shown to display remarkable antimicrobial efficacy towards both planktonic and biofilm cells as the presence of the lipid shell enhanced the interactions with bacterial cells and penetration into biofilms. More work could be done to understand nanoparticle-biofilm interactions; this would help to optimize the LCHNPs further to treat biofilm infections successfully.