Institute of Pharmacy, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Department of Otorhinolaryngology-Head and Neck Surgery, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.
Drug Deliv Transl Res. 2022 Jan;12(1):257-266. doi: 10.1007/s13346-021-00914-9. Epub 2021 Feb 4.
The effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array.
将药物有效递送至内耳仍然是一个未满足的医学需求。由于其位于颞骨内、体积小、屏障紧密且易受损，因此向该感觉器官进行局部控释药物递送极具挑战性。局部内耳内（耳蜗外）药物递送将克服鼓室内（耳蜗外）和全身药物应用的局限性。这种递药系统的要求包括体积小、适当的柔韧性和生物降解性。我们已经开发出基于可生物降解的 PLGA 的植入物，用于控制内耳内药物释放，也可与可植入神经感觉假体（用于听力康复的耳蜗植入物）联合使用。该药物载体系统已在 11 个人类颞骨中进行了内耳植入测试。在其中 5 个人类颞骨中，在插入可生物降解的 PLGA 植入物之前，已植入了来自不同制造商的 CI 阵列。药物载体系统和 CI 阵列通过圆窗被植入到鼓阶。通过超高分辨率计算机断层扫描（µ-CT）对植入的颞骨进行评估，以说明植入电极载体和药物载体系统的位置。µ-CT 测量结果表明，将 PLGA 植入物植入人类内耳的鼓阶并与 CI 阵列联合给药具有可行性。
