高功率密度低频超声间断辐照对载万古霉素骨水泥药物释放的促进作用

Enhancement of intermittent, low-frequency and elevated-intensity insonation on local pharmacoki- netics of vancomycin-loaded bone cement in vitro

目的探讨高功率密度低频超声辐照模式对超声促进药物释放的影响。方法制备质量分数10％的载万古霉素骨水泥（vancomycin-loaded bone cenlent，VLBC）圆柱体试件。随机分为对照组、超声连续辐照组、超声间断辐照组，后两组接受超声辐照14d。浸泡28d内定时测定万古霉素浓度，计算有效抑菌浓度维持时间（T〉MIC）、14～28d亚抑菌浓度释药量、14d内累积释药量并行曲线拟合；浸泡14d后行扫描电镜观察。结果超声间断辐照组T〉MIC。较列照组及超声连续辐照组分别提高6．56d、7．09d，超声连续辐照组较对照组下降0．53d。超声间断辐照组亚抑菌浓度释药量较对照组及超声连续辐照组分别下降0．16mg、0．19mg；14d累积释药量较对照组及超声连续辐照组分别提高2．88mg、2．81mg。三组采用指数增长至最大值模型拟合效果均理想，超声间断辐照组M0、Mmax-M0、K均较对照组及超声连续辐照组提高，超声连续辐照组M0较对照组提高，但Mmax-M0、K、N较对照组降低。结论高功率密度低频超声间断辐照对VLBC的表面释放和内部弥散有明显的促进作用，连续辐照抑制VLBC的内部弥散。

Objective To investigate the effect of intermittent insonation on local drug release and mierostructure of vaneomyein-loaded bone cement （VLBC） in vitro under low-frequency elevated-intensity insonation. Methods Twenty-one VLBC cylindrical specimens were randomly assigned to three groups： a control group, a continuous-insonation group and a intermittent-insonation group. All specimens, from which both insonation groups were insonated for 14 d. During 28 d, the collected PBS from four specimens per group was analyzed with fluorescence polarization immunoassay at designated time intervals, respectively. Four pharmacokinetie parameters, the duration of time for which antimierobial concentration exceed the mini- mum inhibitory concentration （T〉MIC）, the drug release during the first day and between 14 d and 28 d, the cumulative release during 14 d, were all calculated from plots of drug release versus time curve. Exponential rise to maximum model was adopted to fit the plots of drug cumulative release. Three specimens were analyzed with scanning electron microscopy. Results T〉MIC of the intermittent-insonation group increased by 6.56 d and 7.09 d compared with the control group and the continuous-insonation group, respectively. However, T〉MIC of the continuous-insonation group was lower than the control group by 0.53 d. The total release of intermittent-insonation group at sub-inhibitory drug level decreased by 0.16 mg and 0.19 mg compared with the control group and the continuous-insonation group, respectively. The cumulative release of intermittent- insonation group during 14 d increased by 2.88 mg and 2.81 nag compared with the control group and the continuous-insonation group, respectively. M0, Mmax,-M0 and K in intermittent-insonation group significantly increased compared with the control group and the continuous-insonation group. K and N in intermittent-insonation group appeared lower compared with the control group despite increase in M0. Conclusion Our kinetic data and fitting curve confirmed the significant enhancement of intermittent insonation with low-fre- quency elevated-intensity insonation on surface liberation and internal diffusion of drug from VLBC.