Effect Of Low-Frequency Ultrasound On Vancomycin-Loaded Bone Cement From Pharmacological And Bacteriological Investigation

Objective: To investigate the effect of low-frequency ultrasound on the release of vancomycin from ALBC and its regularity in vitro and in vivo. Methods: ALBC specimens were successfully manufactured for in vitro and in vivo assays. 5 w/w % and 10 w/w % 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 immersions in PBS of 40 ml for 8 h the four ultrasound groups were exposed to a timed local ultrasonic field with the drug concentrations assayed for a 2.5-h period and on the 24th hour after the immersion. Sixteen healthy New Zealand White rabbits, with an average weight of (1.86±0.46) kg, were divided randomly into two groups: the ultrasound group was exposed to a local timed intermittent ultrasound field and the control group not. Samples of drainage fluid and urine were collected at programmed intervals during a 5-d period, and the ALBC specimens were extracted from rabbits four weeks after implantations with all their concentrations measured by fluorescence polarization immunoassay (FPIA). Results: The cumulative concentration of vancomycin additionally increased by 71.77% and 73.62% in 10 w/w % specimens and 13.03% and 23.78% in 5 w/w% specimens during a 24 h period in vitro, caused by a 30-min exposure of ultrasound with an intensity of 100 mW/cm~2 and 300 mW/cm~2, respectively. 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 w/w % specimens during a 1-d period and a 5-d period in vivo, respectively, caused byintermittent 30-min exposures of ultrasound with an intensity of 300 mW/cm2. Also, the duration of local subinhibitory concentration decreased by approximately 1 d in the ultrasound group compared to the control group. 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 vancomycin release of ALBC.