The application of ultrasound and microbubble for drug delivery in the inner ear system

• Main Authors: Yu-Fan Shih, 施俞帆
• Other Authors: Ai-Ho Liao
• Format: Others
• Language: zh-TW
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/u98p3k

碩士 === 國立臺灣科技大學 === 醫學工程研究所 === 100 === Purpose: direct drug delivery into inner ear can be achieved by three approaches: (1) diffusion of drug through round window; (2) injection of drug through round window; (3) cochleostomy or canalostomy. The latter two approaches are invasive and have the risk of hearing loss and vertigo. Drug diffusion through round window is only the noninvasive approach. However, how to enhance drug diffusion and how to noninvasively promote drug delivery through round window are two issues that need to be investigated. Ultrasound microbubbles can be useful in imaging, targeted drug delivery and accelerated blood clot dissolution. The purpose of this study is to investigate whether ultrasound microbubbles can help drug delivery through round window. Materials and Methods: our study had 3 portions 1st portion: FITC was used as the objective delivering into inner ear and the intensity of FITC in the lymph of inner ear was measured. Microbubbles were composed of gas core and human albumin. An opening was made in the tympanic bulla of guinea pig to see the round window. In “soak of the round window (SR)” group, 200μl FITC solution or mixture of microbubbles and FITC was added in the tympanic bulla to soak the round window. In “ultrasound irradiation (US)” group, 200μl FITC solution was added in the tympanic bulla and the round window was irradiated with ultrasound for 2 minutes. In “ultrasound microbubbles (US+MBs)” group, the following procedures were repeated. 200μl mixture of microbubbles and FITC was added in the tympanic bulla and the round window was irradiated with ultrasound for 1 minute. In US+MBs+SR group, the following procedures were repeated. 200μl mixture of microbubbles and FITC was added in the tympanic bulla. The round window was irradiated with ultrasound for 1 minute and subsequently soaked for 4 minutes. 2nd rd portion: In SR and US+MBs+SR groups, hearing function was measured before and after the intervention. 3rd portion: the conjugated gentamicin and texas red (GTTR) was used as the objective delivering into inner ear. After tissue harvesting and preparation, confocal microscopy was used for imaging. Results andDiscussion: The intensity of FITC in US+MBs, US and SR groups are 8793.3±1177.3, 2780.67±1020.65, and 1225.33±303.19. Lymphatic FITC was significantly more intense in US+MBs than US and SR groups. The intensity of FITC inUS+MBs+SR and SR groups are 37815±4330.3 and 2228±405. Lymphatic FITC was significantly more intense in US+MBs+SR than SR group. In confocal imaging, GTTR uptake in saccule, utricle and cochlear basal turn was more in US+MBs+SR than SR group. Hearing threshold shift in 4K, 8K, 16K and 32K was not different between US+MBs+SR and SR groups. In addition, post-intervention hearing function of US+MBs+SR group was not different from pre-intervention. Conclusion: Ultrasound microbubbles could enhance drug delivery into inner ear and did not impair hearing function. It was promising in the medical treatment of inner ear disease.