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

Abstract

Background: The bio lm way of life is a common strategy for bacteria to adapt and gain tolerance towards antibiotic treatments. Up to 80% of all infections are bio lm-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 bio lm infections. Speci cally, lipid-coated hybrid nanoparticles (LCHNPs) were investigated on their capability to deliver antibiotics into bio lms. 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 antibio lm tests were performed to evaluate the antimicrobial e cacy of the LCHNPs.Results: LCHNPs were successfully fabricated with high vancomycin encapsulation e ciency of 48.66%and loading e ciency 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 signi cantly 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 bio lms, Van-LCHNPs eradicated up to 99.99% of the underlying bio lm 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 bio lms.Conclusion: LCHNPs were shown to display remarkable antimicrobial e cacy towards both planktonic and bio lm cells as the presence of the lipid shell enhanced the interactions with bacterial cells and penetration into bio lms. More work could be done to understand nanoparticle-bio lm interactions; this would help to optimize the LCHNPs further to treat bio lm infections successfully.

Advances in inhaled antibiotics for management of respiratory tract infections

“…Hybrid nanoparticles have been designed for the administration of vancomycin, with promising results, as they eradicated 99.9% of biofilm cells. Unlike the former study, they showed activity against planktonic cells [19 ▪▪ ] (Fig. 1).…”

Recent Advances in the Development of Lipid-, Metal-, Carbon-, and Polymer-Based Nanomaterials for Antibacterial Applications

“…Lipid polymer hybrid nanoparticles (LPHNPs) have emerged as a potentially superior nanocomposite delivery system by combining the advantages and mitigating the limitations associated with liposomes and polymeric nanoparticles alone [ 361 , 362 , 363 , 364 , 365 , 366 ]. LPHNPs comprise a biodegradable polymeric core for drug encapsulation, an inner lipid layer surrounding the polymeric core, and an outer polymeric stealth layer ( Figure 11 ).…”

“…Recently, LPHNPs have received great attention in antibacterial applications as efficient drug delivery systems due to their combined advantages of liposomes and polymer nanoparticles [ 361 , 363 , 364 , 365 , 366 , 379 ]. Cai et al have investigated the application of LPHNPs to act as promising antibacterial delivery vehicles for biofilm eradication [ 379 ].…”

“…In one recent experiment, Jaglal et al designed a pH-responsive LPHNP system for co-delivery of vancomycin and 18β-glycyrrhetinic acid, showing its ability to eliminate 75% of MRSA in less than 12 h with the advantage of sustained and rapid release of vancomycin in acidic conditions [ 363 ]. LPHNPs consisting of a poly(lactic-co-glycolic acid) core and a dioleoyl-3-trimethylpropane lipid shell were developed for loading vancomycin and were shown to have prominent antibacterial effect against planktonic S. aureus cells [ 364 ]. In this study, enhanced interactions with bacterial cells and penetration into biofilms was due to the presence of lipid shells.…”

Organically Modified Mesoporous Silica Nanoparticles against Bacterial Resistance

“…Focusing on the development of drug delivery nanoformulations, this integrative approach has been demonstrated to overcome the limitations of independent constituents, such as poor stability, premature cargo leakage before reaching the target, low biocompatibility, poor storage stability, and intolerable toxicity . Hence, a wide variety of multicomponent nanosystems have been implemented for drug delivery, gene therapy, phototherapy, tissue regeneration, vaccines, biomolecule detection, cancer theranostics, and antibacterial therapy. − …”