Research Of The Safety And Effectiveness In Non-focused Ultrasound Influence Round Window Membrane Permeability For Intratympanic Injection Administration

Objective:To investigate the safety of low intensity Non-focused ultrasound(NFU) aid intratympanic injection administration in guinea pigs by using auditory brainstem response(ABR) and cochlear fluorescent staining. Liquid mass spectrometry was used to detect drug concentration in the perilymph, observing pharmacokinetic changes after NFU aid intratympanic injection administration. To clear the effectiveness of NFU aid intratympanic injection administration, and explore the way of its clinical application.Methods:1, Electrophysiological examination:Healthy guinea pigs, ABR threshold and III peak latencies was measured at first, then divided into groups to accept the exposure with different intensity and time of NFU,30 minutes later, ABR threshold and III peak latencies was measured again. The value will be compared, to find whether the NFU exposure occur hearing loss.2, Fluorescent staining observation:The guinea pig in different group exposure to different intensity of NFU in short time, cochlear AO/EB staining, basilar membrane stretched preparation, observe the staining nucleus by fluorescence microscope.3, The liquid phase mass spectrometer examination:We establish the concentration-area curve by the liquid phase mass spectrometer. The dexamethasone solution was injected into the otocyst of guinea pigs, then different intensity NFU exposure were taken.10 minutes later, gather the perilymph for liquid phase mass spectrometer examination, comparing the concentration between groups, observing NFU irradiation’s influence on perilymph drug concentration.Results:1, Electrophysiological examination found that after 1.0 to 3.5 W/cm2 1 MHz NFU irradiate 3 min, guinea pigs’ABR threshold and III peak latencies have no significant change (p>0.05).2, Fluorescent staining observation show that after 1-3.5 W/cm2 1 MHz NFU irradiate 3 min, the turn,middle turn and basic turn’s out hair cell have no obvious damage. It has no statistically differences compared with control group.3, According to the results of liquid phase mass spectrometer examination,2 W/cm2 group’s average drug concentration is 213.07 ng/ml,3 W/cm2 group’s average drug concentration is 568.5 ng/ml,3.5 W/cm2 group’s average drug concentration is 1635.61 ng/ml, and the blank control group’s drug concentration is 86.57 ng/ml. There are statistically differences between each groups, (p<0.05),. Conclusion:1, There are no significant changes of guinea pigs’ABR after 3.5 W/cm2 intensity NFU irradiate in short time. A short time, low intensity NFU exposure is safety for guinea pig’s hearing.2,3.5 W/cm2 intensity NFU short time exposure does not result in guinea pig’s hair cell damage.3, NFU aid can effectively improve the permeability of round window membrane, and also increase the effect of intratympanic injection administration. The extent of the increase was positively related to the intensity of NFU.