Plontke S K, Götze G, Rahne T, Liebau A
Klinik für Hals-, Nasen-, Ohrenheilkunde, Kopf- und Hals-Chirurgie, Martin-Luther-Universität Halle-Wittenberg, Ernst-Grube-Str. 40, 06120, Halle (Saale), Deutschland.
HNO. 2016 Nov;64(11):797-807. doi: 10.1007/s00106-016-0257-0.
Local drug application to the inner ear offers a number of advantages over systemic delivery. Local drug therapy currently encompasses extracochlear administration (intratympanic injection); intracochlear administration, particularly for gene and stem cell therapy; as well as various combinations with auditory neurosensory prostheses, either evaluated in preclinical or clinical studies, or off-label. To improve rehabilitation with cochlear implants (CI), one focus is the development of drug-releasing electrode carriers, e. g., to deliver glucocorticosteroids, antiapoptotic substances, or neurotrophines to the inner ear. By protecting neuronal structures from insertion trauma, reducing fibrosis in the inner ear, and by stimulating growth of neuronal structures in the direction of the electrodes, the performance of CIs should be improved. Controlled drug release after extracochlear or intracochlear application in conjunction with a CI can be achieved by, e.g., use of a biocompatible, resorbable controlled-release drug delivery systems. Two case reports are presented. In order to treat worsened speech discrimination and increased impedance, these CI-wearing patients successfully underwent intracochlear placement of a biocompatible, resorbable drug delivery system for controlled release of dexamethasone. The drug levels reached in inner ear fluids after different types of local drug application strategies can be calculated using computer models. The intracochlear drug concentrations calculated in this way were compared for different dexamethasone application strategies.
与全身给药相比，局部药物应用于内耳具有许多优势。目前局部药物治疗包括鼓室外给药（鼓膜内注射）；鼓室内给药，特别是用于基因和干细胞治疗；以及与听觉神经感觉假体的各种联合应用，这些联合应用已在临床前或临床研究中进行评估，或属于未标明的用法。为了改善人工耳蜗（CI）的康复效果，一个重点是开发药物释放电极载体，例如，向内耳输送糖皮质激素、抗凋亡物质或神经营养因子。通过保护神经元结构免受插入创伤、减少内耳纤维化以及刺激神经元结构向电极方向生长，有望提高人工耳蜗的性能。通过使用生物相容性、可吸收的控释药物递送系统等方法，可以在鼓室外或鼓室内应用人工耳蜗的同时实现药物的控释。本文介绍了两个病例报告。为了治疗言语辨别能力下降和阻抗增加的问题，这些佩戴人工耳蜗的患者成功地在内耳植入了一种生物相容性、可吸收的药物递送系统，用于地塞米松的控释。可以使用计算机模型计算不同类型局部药物应用策略后内耳液中达到的药物水平。对不同地塞米松应用策略计算得到的鼓室内药物浓度进行了比较。
