Praetorius M, Limberger A, Müller M, Lehner R, Schick B, Zenner H P, Plinkert P, Knipper M
Department of Oto-Rhino-Laryngology, University Hospitals of the Saarland, Homburg/Saar, Germany.
Audiol Neurootol. 2001 Sep-Oct;6(5):250-8. doi: 10.1159/000046130.
Local therapy is practiced for middle and inner ear diseases but is usually restricted to cases of ear drum perforation or repeated invasive intratympanic drug application. Perfusion of drugs on the round window or through the scalae of animals using a pump system suggests that the chronic local drug treatment might also be feasible in humans. However, drug delivery systems that are currently on the market involve repeated reimplantation if they are to be used for long-term drug supply. A bone-anchored, totally implantable micro-drug delivery system (MDS) for patient-controlled drug supply has been developed [Lehner et al., 1997]. In this study, we show the first successful long-term in vivo test of the MDS micro-pump in rats. The process of implantation and first functional tests will be described. The biomaterial used to manufacture the delivery system did not cause any inflammation reaction in any of the 9 animals successfully implanted. After activation of the micro-pump, the drug reservoir and port was found to be fluid-tight. Bolus applications of tetrodotoxin (TTX) to the round window induced a transient decrease of evoked brainstem responses. In 2 animals which carried the MDS for more than 8 months the proper functioning of the pumping device was examined in a 2-3 week interval over a 3 month period. The MDS can be autoclaved even after long-term implantation and can then be reused for subsequent implantations. Designed for life-long implantation in humans, the demonstration of an effective long-term drug supply to the inner ear using the MDS provides an encouraging first step towards future long-term drug treatment of the inner ear in humans.
局部治疗适用于中耳和内耳疾病，但通常仅限于鼓膜穿孔或反复进行鼓膜内侵入性药物应用的病例。使用泵系统在动物的圆窗或通过蜗管灌注药物表明，慢性局部药物治疗在人类中可能也是可行的。然而，目前市场上的药物输送系统如果要用于长期药物供应，就需要反复重新植入。已经开发出一种用于患者自控药物供应的骨锚定、完全可植入的微型药物输送系统（MDS）[莱纳等人，1997年]。在本研究中，我们展示了MDS微型泵在大鼠体内首次成功的长期测试。将描述植入过程和首次功能测试。用于制造输送系统的生物材料在成功植入的9只动物中均未引起任何炎症反应。激活微型泵后，发现药物储存器和端口不漏液。向圆窗推注河豚毒素（TTX）可引起诱发脑干反应的短暂下降。在2只携带MDS超过8个月的动物中，在3个月的时间内每隔2-3周检查一次泵装置的正常功能。即使长期植入后，MDS也可进行高压灭菌，然后可重新用于后续植入。设计用于人类的终身植入，使用MDS向内耳提供有效的长期药物供应的证明为未来人类内耳长期药物治疗迈出了令人鼓舞的第一步。
