Lipid-based nanocarriers for enhanced gentamicin delivery: a comparative study of liquid crystal nanoparticles and liposomes against Escherichia coli biofilms

Abstract

Conventional antibiotic therapies often fail to eradicate bacterial biofilms due to limited penetration, altered microenvironments, and the presence of persister cells, contributing to persistent and recurrent infections. As a result,the growing threat of antibiotic-resistant bacteria, particularly those forming biofilms, underscores the urgent need for alternative therapeutic strategies. Lipid-based drug delivery systems have emerged as effective nanocarriers for antimicrobials, offering a promising strategy to combat bacterial biofilms due to their biomimetic properties, biocompatibility, and ability to navigate the complex physical, chemical, and biological barriers posed by biofilms. In this study, we compared liquid crystal nanoparticles (LCNPs) and liposomes as delivery systems for gentamicin (GEN) against Escherichia coli (E. coli ) (ATCC 25922 and ATCC 35218) in both planktonic and biofilm forms. Transmission electron microscopy analysis confirmed the particle size of GEN-loaded LCNPs (~ 200 nm) and GEN-loaded liposomes (~ 160 nm), with cubic-shaped LCNPs and lipid bilayer-structured liposomes which remained stable over three weeks at 4ºC. Loading GEN into lipid-based nanoparticles resulted in a two-fold reduction in minimum inhibitory concentration values, without significantly altering the minimum bactericidal concentration. Notably, GEN-LCNPs led to a significant fourfold (for E. coli ATCC 25922) and threefold (for E. coli ATCC 35218) reduction in inhibitory concentrations in biofilm states compared to unformulated GEN, achieving a minimum biofilm inhibitory concentration (MBIC) of 50 μg/mL and 100 μg/mL (P < 0.0001), respectively. In contrast, liposomes showed only a twofold reduction in MBIC values (100–150 μg/mL) for both bacterial biofilms. GEN-loaded LCNPs also reduced the E. coli ATCC 25922 colony-forming unit count by 5000-fold and 4000-fold, while liposomes with similar particle size did not significantly improve GEN’s antimicrobial activity. Moreover, LCNPs improved GEN efficacy regardless of particle size or Pluronic ® concentration. In conclusion, our findings suggest that GEN-loaded LCNPs demonstrated superior antimicrobial efficacy against E. coli biofilms compared to liposomes, highlighting their potential as effective nanocarriers for combating antibiotic-resistant infections. Graphical Abstract

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