Early Samuel, Yang Rong, Li Xiyu, Zhang Zipei, van der Valk Jens C, Ma Xiaojie, Kohane Daniel S, Stankovic Konstantina M
Eaton-Peabody Laboratories, Department of Otolaryngology - Head and Neck Surgery, Massachusetts Eye and Ear, Boston, MA, United States.
Department of Otolaryngology - Head and Neck Surgery, Harvard Medical School, Boston, MA, United States.
Front Neurol. 2021 Feb 23;12:580392. doi: 10.3389/fneur.2021.580392. eCollection 2021.
Acute otitis media is the most common reason for a visit to the pediatrician, often requiring systemic administration of oral antibiotics. Local drug therapy applied to the middle ear could avoid side effects associated with systemic antibiotic administration, however in the majority of patients this would require drugs to diffuse across an intact tympanic membrane. Experimental methods for testing trans-tympanic drug flux in human tissues would be highly valuable to guide drug therapy development for local drug delivery to the middle ear. A total of 30 cadaveric human temporal bones were characterized by trans-tympanic impedance testing to determine how steps in tissue processing and storage might impact intactness of the tympanic membrane and thus suitability for use in studies of trans-tympanic drug flux. Ciprofloxacin drug solutions of varying concentrations were then applied to the lateral surface of the tympanic membrane in eight samples, and middle ear aspirate was collected over the following 48 h to evaluate trans-tympanic flux to the middle ear. Tissue processing steps that involved extensive tissue manipulation were consistently associated with evidence of microperforations in the tympanic membrane tissue. Maintaining the tympanic membrane within the temporal bone, while using an otologic drill to obtain transmastoid access to the middle ear, was demonstrated as a reliable, non-damaging technique for accessing both lateral and medial surfaces for trans-tympanic flux testing. Results in these bones demonstrated trans-tympanic flux of ciprofloxacin when administered at sufficiently high concentration. The study describes key techniques and best practices, as well as pitfalls to avoid, in the development of a model for studying trans-tympanic drug flux in human temporal bones . This model can be a valuable research tool in advancing progress toward eventual clinical studies for trans-tympanic drug delivery to the middle ear.
急性中耳炎是患儿就诊的最常见原因，通常需要口服抗生素进行全身给药。中耳局部用药可避免全身使用抗生素带来的副作用，然而，对于大多数患者而言，这需要药物透过完整的鼓膜进行扩散。测试人体组织中经鼓膜药物通量的实验方法对于指导中耳局部给药的药物治疗开发具有很高的价值。通过经鼓膜阻抗测试对30块人类尸体颞骨进行表征，以确定组织处理和储存步骤如何影响鼓膜的完整性，进而影响其在经鼓膜药物通量研究中的适用性。然后，在八个样本中将不同浓度的环丙沙星药物溶液应用于鼓膜外侧面，并在接下来的48小时内收集中耳吸出物，以评估经鼓膜进入中耳的通量。涉及广泛组织操作的组织处理步骤始终与鼓膜组织中微穿孔的迹象相关。在颞骨内保留鼓膜，同时使用耳科钻经乳突进入中耳，被证明是一种可靠的、无损伤的技术，可用于经鼓膜通量测试的外侧和内侧表面。在这些颞骨中的结果表明，当给予足够高浓度的环丙沙星时，其经鼓膜通量存在。该研究描述了在开发用于研究人类颞骨经鼓膜药物通量的模型时的关键技术和最佳实践，以及需要避免的陷阱。该模型可成为推进中耳经鼓膜药物递送最终临床研究进展的有价值的研究工具。
