SCIDOT-33. ULTRASOUND-FACILITATED DRUG DELIVERY DEVICE FOR LOCAL DRUG INFUSION AGAINST BRAIN TUMORS

Abstract

Abstract OBJECT Local drug delivery into brain tumor faces a major problem: limitations of distribution. Recently, we have been working to develop a novel treatment strategy delivering chemotherapeutic agents directly into the tumor. Previously, we developed an ultrasound facilitated drug delivery (UFD) system in order to achieve extensive drug distribution (J Neurosurg 124, 2016). Subsequently, we fabricated a second-generation device by analyzing optimal ultrasound generating condition. Here, we tested the intraparenchymal and intratumoral drug distribution using the device. METHODS Resonance frequency of the device was determined by measuring the strength of sound field using hydrophone in water. Using the UFD system, applying resonance frequency, evans blue dye was infused into the striatum of Fisher344 rats. Immediately after the infusion, brains were harvested, quickly frozen, and sectioned to evaluate the distributions of the dye. Similar study was then performed in 9L brain tumor model. RESULTS The second-generation device successfully distributed the dye to the volume 1.5~2 times larger than simple CED with using half the driving voltage than first-generation device. Moreover, the distribution instability, which was a major problem with the first-generation device, was resolved achieving smaller standard deviation. Using multiple resonance frequencies of the device, we found the difference in drug distribution; suggesting the existence of optimal frequencies for brain interstitial drug delivery. This drug delivery strategy also worked in brain tumor model increasing the coverage inside the brain tumor. CONCLUSIONS The second generation UFD device successfully and stably achieved enlarged distribution in the brain parenchyma and in the brain tumor.