Alpha-linolenic acid-modified liposomes associate with and modulate antibiotic activity against Helicobacter pylori

Fatty acids have antimicrobial activity against a wide range of bacteria. We therefore aimed to incorporate omega-3 unsaturated <i>alpha</i>-linolenic acid (αLA) into the membrane of antibiotic-loaded liposomes to create a system with dual antibacterial activity against <i>Helicobacter pylori</i>. Liposomes containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, cholesterol, sphingomyelin and the far-red fluorescent DiD label, with varying content of αLA (mol% to total lipid), were fabricated using the thin film evaporation method and hydrated with PBS or amoxicillin solution. The liposomes were characterized for αLA and amoxicillin content, particle size, membrane fluidity and permeability, prior to their addition to cultures of <i>H. pylori</i> strains and clinical isolates. αLA-modified liposomes enhanced the antibacterial action of amoxicillin against <i>H. pylori</i>, as determined using a viable count method. The liposomal formulation achieved a 3-log reduction in bacterial density, compared to a 1.5- to 2-log reduction by amoxicillin in solution. The application of imaging cytometry revealed a significantly increased association of αLA-modified liposomes with <i>H. pylori</i> cells, compared to non-αLA control liposomes. In conclusion, this study demonstrated, for the first time, that the incorporation of αLA increased the attraction of the liposomes to <i>H. pylori</i> and increased antibiotic potency. This suggests that αLA incorporation into liposomes may not only act as an antimicrobial, but also as a potential <i>in vivo</i> targeting strategy.