Trans-tympanic delivery of antibiotics

项目摘要 AOM是美国儿童抗菌药物处方的最常见原因， 疾病和频繁复发被认为是抗生素使用持续增加的部分原因。 病原菌的耐药性。将活性治疗剂直接局部持续递送至中间部位 用于治疗OM的耳可能允许远高于来自 全身给药，这可以更快和更完全地根除OM细菌， 最大限度地减少全身暴露及其不良影响，特别是耐药细菌的选择。我们有 最近描述了一种含有抗生素和化学渗透增强剂的水凝胶， 增强穿过鼓膜的抗生素通量，以产生穿过鼓膜的足够的抗生素通量。 鼓膜（TM）从一个单一的应用，能够治疗OM。我们随后优化了 该制剂在胶凝性质和对鼓膜的粘附性方面是有效的，并且在 中耳炎我们假设这些制剂也能够预防OM，并减轻生物膜 在中耳形成。在这里，我们提出了一个研究计划，将有助于翻译的概念证明 走向临床现实为此，我们组建了一个多学科和多机构的 与合作的良好记录合作。

PROJECT ABSTRACT AOM is the most common reason for antimicrobial prescribing in US children, and due to the high prevalence of disease and frequent recurrences is believed to be partially responsible for the ongoing increase in antibiotic resistance among pathogenic bacteria. Local, sustained delivery of active therapeutics directly to the middle ear for the treatment of OM could potentially allow for much higher middle ear drug concentrations than from systemic administration, which could allow for a faster and more complete eradication of OM bacteria, while minimizing systemic exposure and its adverse effects, particularly selection of drug-resistant bacteria. We have recently described a hydrogel containing antibiotics and chemical permeation enhancers that was capable of enhancing antibiotic flux across the tympanic membrane, to produce a sufficient flux of antibiotic across the tympanic membrane (TM) from a single application to be able to treat OM. We have subsequently optimized this formulation in terms of gelation properties and adherence to the eardrum, and shown efficacy in a model of otitis media. We hypothesize that these formulations will also be able to prevent OM, and mitigate biofilm formation in the middle ear. Here we propose a research plan that will help in translating that proof-of-concept toward a clinical reality. Toward that end, we have assembled a multidisciplinary and multi-institutional collaboration with a proven track record of working together.