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

文献类型： 外文期刊

第一作者： Zhao, Yi

作者： Zhao, Yi;Liu, Bo;Zhang, Shuang-yi;Wang, Yong-fei;Hasi, Su-rong;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Bai, Yu-ting;Cao, Jin-shan;Mao, Wei;Zhao, Yi;Liu, Bo;Zhang, Shuang-yi;Gong, Zhi-guo;Zhao, Jia-min;Yang, Xiao-lin;Cao, Jin-shan;Mao, Wei;Wang, Yong-fei;Qian, Ying-hong

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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

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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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