Egg yolk-derived low-density lipoprotein: A potential drug delivery system to eradicate intracellular bacteria

Antibiotics have limited capacities to penetrate and eliminate intracellular bacteria. This study developed a drug delivery system to surmount the cell-membrane barrier and achieve efficient intracellular antibiotic accumulation for intracellular-bacterial eradication. Ceftiofur (CEF) was encapsulated in hen egg-yolk-extracted low-density lipoproteins (heLDLs) to generate CEF-heLDLs. Based on preliminary research, the drug-loading efficiency was approximately 44.48 % ± 2.35 % (encapsulation rate, approximately 99.31 % ± 0.63 %). CEF-heLDLs exhibited smaller particle sizes and higher absolute zeta potentials than heLDLs, indicating improved dispersibility and stability. In-vitro analyses demonstrated receptor-mediated uptake of CEF-heLDL, with lysosome colocalization. In-vivo localization analyses in mice showed multiorgan distribution characteristics. In-vitro and in-vivo antibacterial experiments showed that CEF-heLDLs displayed superior antibacterial effects against intracellular Staphylococcus aureus compared with free CEF, significantly damaging bacterial cell walls and decreasing intracellular-bacterial survival rates (P < 0.001). CEF-heLDLs significantly reduced mortality in methicillin-resistant S. aureus-infected mice (P < 0.001) compared with free CEF and improved bacterial-induced leukocytosis (P < 0.001). The CEF-heLDL synthesized in this study effectively delivers CEF into cells. Compared to free CEF, it has significantly enhanced efficacy in eliminating intracellular S. aureus, offering a promising novel approach for eradication of intracellular bacteria.