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.
Int J Pharm. 2021 Feb 1;594:120180. doi: 10.1016/j.ijpharm.2020.120180. Epub 2020 Dec 16.
Drug delivery to the inner ear is an important and very challenging field. The cochlea is protected by several barriers that need to be overcome in the drug delivery process. Local drug delivery can avoid undesirable side effects arising from systemic drug delivery. We developed a biodegradable dexamethasone-loaded Round Window (RW) Disk based on poly(D,L-lactic-co-glycolic acid) (PLGA) for local drug therapy to the inner ear by RW membrane administration by a film-casting method. The optimal drying time was characterized by thermogravimetric analysis and differential scanning calorimetry. In addition, the mass and polymer degradation over time of drug release was measured in vitro showing a total mass loss of 70% after 3 weeks. Dexamethasone release was determined by a RW model setup using a polyethylene terephthalate membrane. We achieved a controlled release over 52 days. Ex vivo implantation of a RW Disk onto a guinea pig RW membrane indicated well-fitting properties of the drug delivery device leading to a close surface contact with the membrane and the successful proof of concept. The developed RW Disks could be new and promising drug delivery device to achieve effective local drug delivery to the inner ear for an extended time.
内耳给药是一个重要且极具挑战性的领域。耳蜗受到多种屏障的保护，这些屏障在药物传递过程中需要克服。局部给药可以避免全身给药引起的不良副作用。我们开发了一种基于聚（D，L-乳酸-共-乙醇酸）（PLGA）的可生物降解的地塞米松负载的圆窗（RW）盘，用于通过 RW 膜给药通过薄膜铸造法进行内耳局部药物治疗。通过热重分析和差示扫描量热法对最佳干燥时间进行了表征。此外，还通过体外测量药物释放的质量和聚合物随时间的降解来测量，在 3 周后总质量损失达到 70%。通过使用聚对苯二甲酸乙二醇酯膜的 RW 模型设置来确定地塞米松的释放。我们实现了超过 52 天的控制释放。将 RW 盘植入豚鼠 RW 膜的离体实验表明，药物输送装置具有良好的适配性能，与膜紧密接触，并成功证明了这一概念。开发的 RW 盘可以成为新的有前途的药物输送装置，以实现有效的局部药物输送到内耳，并延长时间。
