Shen Sarek A, Goyal Mukund Madhav, Lane Kelly, Lehar Mohamed, Sun Daniel Q
Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins School of Medicine;
Department of Chemical and Biomolecular Engineering, Johns Hopkins Whiting School of Engineering.
J Vis Exp. 2024 Feb 23(204). doi: 10.3791/65816.
Efficient and minimally invasive drug delivery to the inner ear is a significant challenge. The round window membrane (RWM), being one of the few entry points to the inner ear, has become a vital focus of investigation. However, due to the complexities of isolating the RWM, our understanding of its pharmacokinetics remains limited. The RWM comprises three distinct layers: the outer epithelium, the middle connective tissue layer, and the inner epithelial layer, each potentially possessing unique delivery properties. Current models for investigating transport across the RWM utilize in vivo animal models or ex vivo RWM models which rely on cell cultures or membrane fragments. Guinea pigs serve as a validated preclinical model for the investigation of drug pharmacokinetics within the inner ear and are an important animal model for the translational development of delivery vehicles to the cochlea. In this study, we describe an approach for explantation of a guinea pig RWM with surrounding cochlear bone for benchtop drug delivery experiments. This method allows for preservation of native RWM architecture and may provide a more realistic representation of barriers to transport than current benchtop models.
高效且微创地向内耳给药是一项重大挑战。圆窗膜(RWM)作为进入内耳的少数入口点之一,已成为重要的研究焦点。然而,由于分离RWM的复杂性,我们对其药代动力学的理解仍然有限。RWM由三个不同的层组成:外层上皮、中间结缔组织层和内层上皮层,每层可能都具有独特的给药特性。目前用于研究药物穿过RWM转运的模型采用体内动物模型或依赖细胞培养或膜片段的离体RWM模型。豚鼠是用于研究内耳药物药代动力学的经过验证的临床前模型,也是向耳蜗递送载体转化开发的重要动物模型。在本研究中,我们描述了一种用于在台式给药实验中取出带有周围耳蜗骨的豚鼠RWM的方法。这种方法能够保留天然RWM结构,并且与当前的台式模型相比,可能更真实地反映转运屏障。