Liu Tiexin, Lin Junqing, Zheng Xianyou
Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China.
National Orthopedic Medical Center, Shanghai, 200233, P. R. China.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2025 Mar 15;39(3):362-369. doi: 10.7507/1002-1892.202412031.
To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly- -lysine (ε-PLL) and cyclodextrin (CD) (ε-PLL-CD-LZD), aiming to enhance antibiotic bioavailability, effectively penetrate and disrupt biofilm structures, and thereby improve the treatment of bone and joint infections.
ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. biocompatibility was evaluated through live/dead cell staining after co-culturing with mouse embryonic osteoblast precursor cells (MC3T3-E1), human umbilical vein endothelial cells, and mouse embryonic fibroblast cells (3T3-L1). The biofilm-enrichment capacity of ε-PLL-CD-LZD was assessed using biofilms through enrichment studies. Its biofilm eradication efficacy was investigated via minimum inhibitory concentration (MIC) determination, scanning electron microscopy, and live/dead bacterial staining. A bone and joint infection model in male Sprague-Dawley rats was established to validate the antibacterial effects of ε-PLL-CD-LZD.
In ε-PLL-CD-LZD, the average grafting rate of CD reached 9.88%. The cell viability exceeded 90% after co-culturing with three types cells. The strong biofilm enrichment capability was observed with a MIC of 2 mg/L. Scanning electron microscopy observations revealed the effective disruption of biofilm structure, indicating potent biofilm eradication capacity. rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site ( <0.05).
The ε-PLL-CD antibiotic delivery system provides a treatment strategy for bone and joint infections with high clinical translational significance. By effectively enhancing antibiotic bioavailability, penetrating, and disrupting biofilms, it demonstrated significant anti-infection effects in animal models.
探索基于ε-聚赖氨酸（ε-PLL）和环糊精（CD）的利奈唑胺（LZD）靶向细菌生物膜的抗生素递送系统（ε-PLL-CD-LZD）的作用机制，旨在提高抗生素的生物利用度，有效穿透并破坏生物膜结构，从而改善骨与关节感染的治疗效果。
通过化学方法合成ε-PLL-CD-LZD。采用核磁共振表征CD的接枝率。与小鼠胚胎成骨细胞前体细胞（MC3T3-E1）、人脐静脉内皮细胞和小鼠胚胎成纤维细胞（3T3-L1）共培养后，通过活/死细胞染色评估其生物相容性。通过富集研究，利用生物膜评估ε-PLL-CD-LZD的生物膜富集能力。通过最低抑菌浓度（MIC）测定、扫描电子显微镜和活/死细菌染色研究其生物膜根除效果。建立雄性Sprague-Dawley大鼠骨与关节感染模型，以验证ε-PLL-CD-LZD的抗菌效果。
在ε-PLL-CD-LZD中，CD的平均接枝率达到9.88%。与三种类型细胞共培养后，细胞活力超过90%。观察到其具有较强的生物膜富集能力，MIC为2 mg/L。扫描电子显微镜观察显示生物膜结构被有效破坏，表明其具有强大的生物膜根除能力。大鼠实验表明，ε-PLL-CD-LZD显著降低了病变部位的细菌载量和感染阳性率（P<0.05）。
ε-PLL-CD抗生素递送系统为骨与关节感染提供了一种具有高度临床转化意义的治疗策略。通过有效提高抗生素生物利用度、穿透并破坏生物膜，其在动物模型中显示出显著的抗感染效果。
