低频超声对万古霉素骨水泥药物释放的影响

Effect of ultrasound on drug release of vancomycin-loaded acrylic bone cement

目的在体外和动物体内条件下研究低频超声对抗生素骨水泥(antibiotic-loadedbonecement,ALBC)的促释放作用及其规律。方法制作载万古霉素ALBC的体外试件和体内试件。分别将质量分数为5%和10%的ALBC体外试件随机分为对照组、100mW/cm2超声组和300mW/cm2超声组。所有试件于40mlPBS中浸泡8h后,超声组接受超声干预30min,观察浸泡24h内药物累积浓度的变化。另取健康新西兰大白兔16只,将质量分数为7.5%的ALBC植入髋关节后随机分为对照组和超声组,每组8只。超声组于术后不同时间接受超声干预30min(300mW/cm2),术后5d内定时检测引流液和尿液中万古霉素浓度,术后4周检测ALBC残余药量。结果体外条件下10%100mW/cm2超声组和10%300mW/cm2超声组在浸泡24h后的药物释放分别较10%对照组增加71.77%、73.62%,5%100mW/cm2超声组和5%300mW/cm2超声组分别较5%对照组增加13.03%、23.78%。超声强度和药物载荷均显著增加ALBC的药物释放。体内条件下超声组药物释放量在术后1d和5d分别较对照组高148.18%(t=3.510,P<0.01)和82.39%(t=2.345,P<0.05),术后4周超声组ALBC药物溶出低于对照组(t=3.697,P<0.01)。结论低频连续型超声能促进和加快ALBC的药物释放。

Objective To investigate the effect of low-frequency ultrasound on the release of vancomycin from antibiotic-loaded bone cement （ALBC） and its regularity in vitro and in vivo. Methods ALBC specimens were successfully manufactured for in vitro and in vivo assays. 5% and 10% ALBC specimens were both randomly divided into three groups： the control group, 100 mW/cm^2 ultrasound group and 300 mW/cm^2 ultrasound group. After immersing in PBS of 40 ml for 8 h, the four ultrasound groups were exposed to a timed local ultrasonic field for 30 rain, then the drug cumulative concentrations were observed during a 2.5 h period after exposure and on the 24th hour after immersion. Sixteen healthy New Zealand white rabbits were divided randomly into two groups： the ultrasound group was exposed to a local timed intermittent ultra- sound field and the control group not. Samples of drainage fluid and urine were collected at programmed in- tervals during a 5 d period, and the ALBC specimens were extracted from rabbits four weeks after implanta- tions with all their concentrations measured by fluorescence polarization immunoassay （FPIA）. Results Af- ter immersing 24 h in vitro, the cumulative concentration of vancomycin additionally increased by 71.77% and 73.62% in 10% 100 mW/cm^2 ultrasound group and 300 mW/cm^2 group respectively comparing with 10% control group; while increased 13.03% and 23.78% in 5% 100 mW/cm^2 and 300 mW/cm^2 groups comparing with 5% control group. Furthermore, the total release was positively correlated with the ultrasound intensity （P〈 0.05） and the amount of vancomycin loaded in specimens （P〈 0.01）. The total release of vancomycin increased by 148.18% （P〈 0.01） and 82.39% （P〈 0.05） in 7.5% specimens during a 1 d period and a 5 d period in vivo, respectively, caused by intermittent 30 min exposures of ultrasound with an intensity of 300 mW/cm^2. More decreased residue of vancomycin was detected in the ultrasound group than in the control group four weeks after implantations （P〈 0.01）. Conclusion Low-frequency low-intensity continuous ultrasound may provide an effective method to enhance and accelerate the vancomvcin release of ALBC.