The roles of lipid in anti-biofilm efficacy of lipid-polymer hybrid nanoparticles encapsulating antibiotics

Owing to their physical robustness, lipid-polymer hybrid nanoparticles are developed to potentially replace liposomes, which possess high affinity towards biofilm cells, as antibiotic delivery vehicles in lung biofilm infection therapy. Towards this aim, antibacterial activity of antibiotic-loaded hybrid nanoparticles is examined in vitro against Pseudomonas aeruginosa biofilm cells for two pharmaceutical dosage forms of the nanoparticles - aqueous suspension and dry-powders. Anti-biofilm efficacy of the hybrid nanoparticles is compared to that of polymeric nanoparticles to elucidate the impact of lipid inclusion, if any, on biofilm eradication. Poly (lactic-co-glycolic acid), phosphatidylcholine, and levofloxacin are employed as the polymer, lipid, and antibiotic models, respectively. Compared to polymeric nanoparticles, hybrid nanoparticles are similar in size but more stable. The presence of lipid coat in the hybrid nanoparticles results in slower antibiotic release rates, but it does not improve their biofilm affinity. Hybrid nanoparticles exhibit higher antibacterial efficacy against biofilm cells, but not against planktonic cells shed from the biofilm matrix. Variations in the antibiotic activity, release rate, and biofilm cell detachment between the polymeric and hybrid nanoparticles have been ruled out as factors contributing to the higher anti-biofilm efficacy. Follow-up studies beyond antibiotic susceptibility testing are needed to identify the mechanisms for the anti-biofilm enhancement by hybrid nanoparticles.