Ohmline lipid platform: a dual antimicrobial and nanocarrier strategy to potentiate antibiotic efficacy

Abstract

The global rise of antimicrobial resistance has significantly reduced the effectiveness of conventional antibiotics, highlighting the urgent need for alternative and complementary therapeutic strategies. Nanotechnology-based drug delivery systems, particularly lipid nanoparticles, have emerged as promising tools to enhance antibiotic efficacy while limiting toxicity and resistance development. In this study, we evaluated the antimicrobial activity and drug carrier potential of Ohmline, a novel alkyl-ether glycolipid capable of self-assembling into nanotubes and lipid nanoparticles. First, a wide range of Gram-positive and Gram-negative bacteria were used to test Ohmline nanotubes antibacterial activity. All examined strains were partially inhibited, with a more noticeable effect on Gram-positive bacteria. Then, the synergistic potential of Ohmline combined with commercially available antibiotics (ampicillin, ceftriaxone, and ciprofloxacin) was evaluated using two different approaches: binary mixtures of Ohmline nanotubes and antibiotics and microfluidically produced Ohmline:DMPC (75:25) nanoparticles with the antibiotics encapsulated. Binary formulations demonstrated strong, strain-dependent synergistic effects at sub-MIC antibiotic concentrations, particularly against Enterococcus faecalis and Citrobacter braakii. Notably, antibiotic encapsulation within Ohmline nanoparticles further enhanced antimicrobial efficacy compared to non-encapsulated combinations, achieving near-complete growth inhibition in E. faecalis and significant inhibition in Klebsiella pneumoniae and C. braakii. Overall, our findings demonstrate that Ohmline possesses intrinsic antibacterial activity and acts as an effective lipid nanocarrier that potentiates antibiotic action. The dual functionality of Ohmline supports its potential as a versatile building block for next-generation antimicrobial formulations.