Department of Pharmaceutical Sciences, Università degli Studi di Milano, Via G. Colombo, 71, 20133, Milan, Italy.
Drug Deliv Transl Res. 2018 Apr;8(2):436-449. doi: 10.1007/s13346-017-0384-5.
The sense of hearing is essential for permitting human beings to interact with the environment, and its dysfunctions can strongly impact on the quality of life. In this context, the cochlea plays a fundamental role in the transformation of the airborne sound waves into electrical signals, which can be processed by the brain. However, several diseases and external stimuli (e.g., noise, drugs) can damage the sensorineural structures of cochlea, inducing progressive hearing dysfunctions until deafness. In clinical practice, the current pharmacological approaches to treat cochlear diseases are based on the almost exclusive use of systemic steroids. In the last decades, the efficacy of novel therapeutic molecules has been proven, taking advantage from a better comprehension of the pathological mechanisms underlying many cochlear diseases. In addition, the feasibility of intratympanic administration of drugs also permitted to overcome the pharmacokinetic limitations of the systemic drug administration, opening new frontiers in drug delivery to cochlea. Several innovative drug delivery systems, such as in situ gelling systems or nanocarriers, were designed, and their efficacy has been proven in vitro and in vivo in cochlear models. The current review aims to describe the art of state in the cochlear drug delivery, highlighting lights and shadows and discussing the most critical aspects still pending in the field.
听觉对于人类与环境进行交互至关重要，其功能障碍会严重影响生活质量。在这方面，耳蜗在将空气传播的声波转换为可被大脑处理的电信号方面起着至关重要的作用。然而，一些疾病和外部刺激（例如噪音、药物）会损害耳蜗的感觉神经结构，导致听力逐渐受损，直至耳聋。在临床实践中，目前治疗耳蜗疾病的药理学方法几乎完全依赖于全身类固醇的使用。在过去的几十年中，新型治疗分子的疗效已得到证实，这得益于对许多耳蜗疾病病理机制的更好理解。此外，通过药物鼓室内给药的可行性也克服了全身药物给药的药代动力学限制，为耳蜗给药开辟了新的前沿。已经设计了几种创新的药物传递系统，例如原位凝胶系统或纳米载体，并在耳蜗模型中进行了体外和体内研究，证明了其疗效。本综述旨在描述耳蜗药物传递的最新进展，突出优点和缺点，并讨论该领域仍存在的最关键问题。
