Egg yolk-derived low-density lipoprotein: A potential drug delivery system to eradicate intracellular bacteria
文献类型： 外文期刊
作者： Zhao, Yi 1 ; Liu, Bo 1 ; Zhang, Shuang-yi 1 ; Wang, Yong-fei 1 ; Hasi, Su-rong 1 ; Qian, Ying-hong 4 ; Gong, Zhi-guo 1 ; Zhao, Jia-min 1 ; Yang, Xiao-lin 1 ; Bai, Yu-ting 1 ; Cao, Jin-shan 1 ; Mao, Wei 1 ;
作者机构： 1.Inner Mongolia Agr Univ, Coll Vet Med, Lab Vet Clin Pharmacol, 29 Erdosdong Rd, Hohhot 010011, Peoples R China
2.Inner Mongolia Agr Univ, Key Lab Clin Diag & Treatment Tech Anim Dis, Minist Agr, 29 Erdosdong Rd, Hohhot 010011, Peoples R China
3.Inner Mongolia Med Univ, Hohhot 010030, Peoples R China
4.Inner Mongolia Acad Agr & Anim Husb Sci, Hohhot 010010, Peoples R China
关键词： Hen egg low-density lipoprotein; Ceftiofur; Intracellular drug delivery system; Staphylococcus aureus
期刊名称：INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES （ 影响因子：8.5； 五年影响因子：8.7 ）
ISSN： 0141-8130
年卷期： 2025 年 306 卷
页码：
收录情况： SCI
摘要： 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 lowdensity 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 %). CEFheLDLs 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.
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