亚胺培南西司他丁抗生素骨水泥的体外药物释放试验和力学测试

In Vitro Drug Release and Mechanical Testing of Imipenem Cilastatin Antibiotic-loaded Bone Cement

目的探讨不同浓度亚胺培南西司他丁抗生素骨水泥缓释载体的体外释放速率和抑菌效果,以及对骨水泥力学性能的影响,为慢性骨髓炎的临床治疗提供实验依据。方法先制备不同浓度的亚胺培南西司他丁梯度溶液,采用三重四级杆液质联用仪(Liquid Chromatograph Mass Spectrometer,LC-MS)进行检测,分别得出亚胺培南和西司他丁2条标准曲线方程。用亚胺培南西司他丁与骨水泥按质量1∶40、4∶40、8∶40(g∶g),制备低、中、高浓度组的亚胺培南西司他丁骨水泥,进行体外释放试验,检测1、3、7、14、21、28、35 d的释放速率。采用低、中、高浓度组的亚胺培南西司他丁骨水泥分别对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌进行抑菌试验,记录1、2、3、4、5、6 d的抑菌环直径。另外检测不同浓度的亚胺培南西司他丁骨水泥抗压力学性能。结果亚胺培南标准曲线方程Y=0.001X-0.0088(R2=0.9989),西司他丁标准曲线方程Y=0.0026X+0.0281(R^(2)=0.9999)。在不同时间点,亚胺培南西司他丁骨水泥的释放速率,低浓度组<中浓度组<高浓度组,差异具有统计学意义(P<0.001)。对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌的抑菌环直径,低浓度组<中浓度组<高浓度组,差异具有统计学意义(P<0.05)。随着添加亚胺培南西司他丁的质量越多,骨水泥的抗压强度越低(P<0.05)。结论制备的亚胺培南西司他丁抗生素骨水泥,随着亚胺培南西司他丁浓度的增加,释放速率更快,抗菌效果更好,但抗压能力降低。

Objective To explore the in vitro release rate and antibacterial effect of imipenem cilastatin antibiotic-loaded bone cement sustained-release carriers with different concentrations,as well as their impact on the mechanical properties of bone cement,in order to provide experimental evidence for the clinical treatment of chronic osteomyelitis.Method Different concentrations of antibio∶tic gradient solutions were prepared for Liquid Chromatograph Mass Spectrometer(LC-MS)detection,and two standard curve equations were obtained for imipenem and cilastatin respectively.Sustained-release carriers for low,medium,and high concentration groups were prepared by using imipenem cilastatin and bone cement at a mass ratio of 1:40,4:40,and 8:40(g:g),and in vitro release tests to detect the release rates were conducted at 1,3,7,14,21,28,and 35 days.Antibiotic bone cement with low,medium,and high concentration groups was used to conduct antibacterial tests on Staphylococcus aureus,Escherichia coli,and Pseudomonas aeruginosa,and the diameter of the antibacterial rings were recorded at 1,2,3,4,5,and 6 days.In addition,the compressive strength of bone cement with different concentrations of antibiotics was tested.Result The standard curve equations for imipenem and cilastatin obtained in this experiment were Y=0.001X-0.0088(R²=0.9989)and Y=0.0026 X+0.0281(R^(²)=0.9999),respectively.At different time points,the release rates of imipenem cisplatin bone cement were smaller in the low concentration group than in the medium concentration group,and smaller in the medium concentration group than in the high concentration group,with statistically significant differences(P<0.001).The diameters of the antibacterial ring against Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa were shorter in the low concentration group than in the medium concentration group,and shorter in the medium concentration group than in the high concentration group,and the difference was statistically significant(P<0.05).As the amount of imipenem cilastatin added increased,the compressive strength of bone cement gradually decreased(P<0.05).Conclusion The prepared imipenem-cilastatin bone cement was observed to exhibit a faster release rate and a more enhanced antibacterial effect with the increase of imipenem-cilastatin concentration,but its compressive strength decreased.