Role of antibiotic delivery system targeting bacterial biofilm based on ε-poly- L-lysine and cyclodextrin in treatment of bone and joint infections.
10.7507/1002-1892.202412031
- Author:
Tiexin LIU
1
;
Junqing LIN
1
;
Xianyou ZHENG
1
Author Information
1. Department of Orthopedics, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200233, P. R. China.
- Publication Type:Journal Article
- Keywords:
Bone and joint infections;
antibiotic delivery;
biofilm;
cyclodextrin;
rat;
ε-poly-L-lysine
- MeSH:
Biofilms/drug effects*;
Animals;
Anti-Bacterial Agents/pharmacology*;
Polylysine/chemistry*;
Cyclodextrins/administration & dosage*;
Humans;
Linezolid/pharmacology*;
Staphylococcus aureus/physiology*;
Rats, Sprague-Dawley;
Mice;
Rats;
Male;
Drug Delivery Systems;
Staphylococcal Infections/drug therapy*;
Microbial Sensitivity Tests;
Human Umbilical Vein Endothelial Cells;
Osteoblasts/cytology*
- From:
Chinese Journal of Reparative and Reconstructive Surgery
2025;39(3):362-369
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE:To explore the mechanism of antibiotic delivery system targeting bacterial biofilm with linezolid (LZD) based on ε-poly- L-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.
METHODS:ε-PLL-CD-LZD was synthesized via chemical methods. The grafting rate of CD was characterized using nuclear magnetic resonance. In vitro 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 Staphylococcus aureus 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.
RESULTS: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. In vivo rat experiments demonstrated that ε-PLL-CD-LZD significantly reduced bacterial load and infection positivity rate at the lesion site ( P<0.05).
CONCLUSION: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.
