Rossi Shawn, Azghani Ali O, Omri Abdelwahab
Department of Chemistry and Biochemistry, Laurentian University, 935 Ramsey Lake Road, Sudbury, Ontario, Canada P3E 2C6.
J Antimicrob Chemother. 2004 Dec;54(6):1013-8. doi: 10.1093/jac/dkh477. Epub 2004 Nov 10.
Failure of orthopaedic devices, mainly femoral hip replacements, due to infection is of increasing medical importance. There is a need for improved antibiotic delivery systems in the treatment of orthopaedic infections and here we have evaluated polyhydroxyalkanoate formulations for their suitability as a constant delivery system for gentamicin.
Gentamicin was incorporated in poly(hydroxybutyric-co-hydroxyvalerate) (PHBV) with 8% or 12% hydroxyvalerate (HV) content at 2:1 or 5:1 (weight to weight) ratio. In conjunction with an elution study, a scanning electron microscopy and a porosity study were carried out to explore physical characteristics of the complexes before and after the leaching effect. The antibacterial effectiveness of the complexes was analysed in a bacterial adhesion assay using clinical isolates of Staphylococcus haemolyticus and Staphylococcus aureus. In addition, the polymers were exposed to pooled human blood to test their biocompatibility in both static and dynamic environments.
We have shown that increasing the HV content from 8% to 12% leads to a faster release of the integrated antibiotic. An increase in antibiotic content enhanced the homogeneity while decreasing the permeability of the complexes and reducing the release rate. A significant reduction in the number of the adherent S. aureus and gentamicin-resistant S. haemolyticus within a 48 h exposure to our formulations confirmed the effectiveness of the PHBV/gentamicin complexes. Finally, these formulations did not alter the haemodynamics of the pooled blood samples after an extended period of time.
Taken together, the PHBV/gentamicin formulations may prove to be effective preventive therapeutic modalities in implant-related Staphylococcus infections.
因感染导致的骨科器械（主要是股骨髋关节置换物）失效在医学上的重要性日益增加。在治疗骨科感染方面，需要改进抗生素递送系统，在此我们评估了聚羟基脂肪酸酯制剂作为庆大霉素持续递送系统的适用性。
将庆大霉素以2:1或5:1（重量比）的比例掺入羟基戊酸含量为8%或12%的聚（羟基丁酸 - 共 - 羟基戊酸）（PHBV）中。结合洗脱研究，进行扫描电子显微镜和孔隙率研究，以探究浸出作用前后复合物的物理特性。使用溶血葡萄球菌和金黄色葡萄球菌的临床分离株，通过细菌黏附试验分析复合物的抗菌效果。此外，将聚合物暴露于混合人血中，以测试其在静态和动态环境中的生物相容性。
我们已表明，将羟基戊酸含量从8%增加到12%会导致整合抗生素的释放更快。抗生素含量的增加提高了均匀性，同时降低了复合物的渗透性并降低了释放速率。在暴露于我们的制剂48小时内，金黄色葡萄球菌和耐庆大霉素溶血葡萄球菌的黏附数量显著减少，证实了PHBV/庆大霉素复合物的有效性。最后，经过较长时间后，这些制剂并未改变混合血样的血流动力学。
综上所述，PHBV/庆大霉素制剂可能被证明是植入相关葡萄球菌感染有效的预防性治疗方式。
