Intracellular delivery, accumulation, and discrepancy in antibacterial activity of four enrofloxacin-loaded fatty acid solid lipid nanoparticles

[Display omitted] •Docosanoic acid solid lipid nanoparticles improved loading capacity and encapsulation efficiency.•The four fatty acid solid lipid nanoparticles showed low cytotoxicity.•Docosanoic acid solid lipid nanoparticles improved cellular uptake and intracellular retention.•Docosanoic acid solid lipid nanoparticles improved activity of enrofloxacin against intracellular Salmonella. Four fatty acid-solid lipid nanoparticles (SLNs) were formulated and evaluated for intracellular delivery, accumulation, as well as discrepancy in antimicrobial efficacy of their loaded enrofloxacin by using RAW 264.7 cells. The delivery efficacy of enrofloxacin into the macrophages by docosanoic acid SLNs (DAS), octadecanoic acid SLNs (OAS), hexadecanoic acid SLNs (HAS), and tetradecanoic acid SLNs (TAS) were 26.1–29.0, 9.3–10.3, 4.7–5.3 and 4.5–5.0 folds, respectively, compared to free drug when co-incubation for 0.25−4 h. The longer fatty acid prepared nanoparticles loaded enrofloxacin eliminated more slowly and accumulated in the cells for a longer time.The confocal microscopy also demonstrated that higher amount of fatty acid SLNs entered the cells with stronger accumulation performance and less amount SLNs absorbed on the cytomembrane as the carbon chain of fatty acids increased. The bactericidal activity of the four fatty acid SLNs against intracellular Salmonella CVCC541 significantly enhanced compared to the free enrofloxacin. These results revealed that fatty acid SLNs, especially docosanoic acid nanoparticles, might be effective nanocarriers to ferry enrofloxacin or other lipid soluble drugs into cells for intracellular bacterial infection treatment.