Targeting bacteria, the innate response of the middle ear to infection, and host-pathogen interactions, using topical and transtympanic applications for the treatment of otitis media.

针对细菌、中耳对感染的先天反应以及宿主与病原体的相互作用，使用局部和经鼓膜应用来治疗中耳炎。

• 批准号: 9769495
• 负责人: Patricia Ann Schachern
• 金额: $ 21.76万
• 依托单位: EARNANO, LLC
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-13 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9769495
• 关键词: 1 year old; 5 year old; Acute; Adrenal Cortex Hormones; Affect; Age; Alteplase; Anti-Bacterial Agents; Antibiotic Therapy; Antibiotics; Area; Bacteria; Bacterial Antibiotic Resistance; Binding Proteins; Biological Availability; Biomass; Businesses; Caring; Cells; Chemicals; Child; Childhood; Chinchilla (genus); Chronic; Combined Antibiotics; Consequentialism; Containment; DNA; Development; Dexamethasone; Diagnosis; Diffuse; Dimethyl Sulfoxide; Disclosure; Disease; Drug Combinations; Drug Delivery Systems; Ear; Ear Diseases; Encapsulated; Enhancers; Ensure; Epidermis; Exposure to; Fibrin; Fibrinolytic Agents; Formulation; Gel; Health; Host Defense; Human; Immune Evasion; Immune response; Infection; Infiltration; Inflammatory; Inflammatory Response; Innate Immune Response; Iron; Labyrinth; Lactoferrin; Magnetism; Mediating; Medical; Membrane; Membrane Proteins; Methods; Microbial Biofilms; Modality; Mucous Membrane; Office Visits; Oral; Organ; Otitis Media; Otitis Media with Effusion; Parents; Penetration; Phagocytes; Pharmaceutical Preparations; Pharmacological Treatment; Pharmacology; Phosphate Buffer; Population; Predisposition; Proteins; Recurrence; Research; Risk; Sensory; Site; Skin; Solvents; Streptococcus pneumoniae; Structure; Surface; System; Temporal bone structure; Testing; Text; Therapeutic; Time; Topical application; Treatment Efficacy; Tympanic membrane; Virulence; Virulent; Visit; Water; antimicrobial peptide; bacterial resistance; base; chronic infection; clinical Diagnosis; commercialization; design; direct application; disease diagnosis; efficacy testing; effusion; experience; extracellular; improved; innovation; middle ear; mutant; neutrophil; ototoxicity; particle; pathogen; prevent; relating to nervous system; response; round window; scaffold; socioeconomics; success

Otitis media is a world-wide disease primarily affecting the pediatric population under the age of 5 years. It is the most common reason for pediatric care visits and antibiotic therapy. Over-prescription and poor- compliance have led to a reduced susceptibility of bacteria to antibiotics and, consequentially, to recurrent and chronic ear diseases. Clearly, there is a compelling need to investigate alternative therapeutic modalities. The middle ear is a large cavity. It makes use of components of the innate immune response to trap bacteria, containing them for elimination by phagocytes. However, these components can also encapsulate bacteria and protect them by immune evasion. We will investigate the efficacy of a formulation for the treatment of otitis media that targets both the innate response of the middle ear to infection and the pathogen. We will first target host containment of bacteria to expose them to treatment. Treatment consists of a potent antimicrobial peptide and a key molecule of the early innate response of the middle ear mucosa to infection. Bacteria will also be treated with an antibiotic/corticosteroid. Bacterial resistance is a world-wide health concern. We believe that our combination of antibiotic and non-antibiotic modalities will be successful in eliminating bacteria in the middle ear, thereby helping to prevent recurrent and chronic infections. Not only is there a need to challenge traditional pharmacologic treatments, but to develop non-traditional methods of administration as well. The conventional method of treating otitis media with oral antibiotics exposes other organs to the treatment, as well as the middle ear. Topical treatment would be ideal in that it would limit treatment to the middle ear and provide a greater concentration of the pharmacologic agent to the infected area. And because the treatment is administered as an eardrop, it can be applied at time of diagnosis, thus ensuring compliance. Like the skin, the tympanic membrane is impermeable to most substances, necessitating a penetration enhancement vehicle. A number of these have been studied, but with limited success. We are using a penetration enhancement vehicle that has been well characterized. It has been shown to pass the epidermis of the skin via pore formation, and so should likely pass the epidermis of the tympanic membrane. Moreover, it is not ototoxic to the sensory-neural structures of the inner ear. Otitis media is world-wide health concern that has broad-reaching medical and socioeconomic challenges. We have designed a drug intended to more effectively eliminate bacteria from the middle ear in the acute stages of otitis media, preventing recurrent and chronic infections. We are likewise investigating its topical transtympanic administration with a penetration enhancement vehicle that is a powerful solvent with potential for use in the treatment of otitis media and other ear diseases.

中耳炎是一种世界性的疾病，主要影响5岁以下的儿科人群。它 是儿科就诊和抗生素治疗的最常见原因。处方药过量和贫穷- 依从性降低了细菌对抗生素的敏感性，因此， 慢性耳部疾病显然，迫切需要研究替代治疗方式。 中耳是一个很大的空腔。它利用先天免疫反应的组成部分， 细菌，含有它们以被吞噬细胞消除。但是，这些组件也可以封装 并通过免疫逃避来保护它们。 我们将研究用于治疗中耳炎的制剂的功效，该制剂靶向先天性中耳炎和先天性中耳炎。 中耳对感染和病原体的反应。我们将首先针对细菌的宿主遏制， 让他们接受治疗治疗包括一种有效的抗菌肽和一种早期免疫缺陷的关键分子。 中耳粘膜对感染的先天反应。细菌也将被处理， 抗生素/皮质类固醇。细菌耐药性是一个全球性的健康问题。我们相信我们的组合 抗生素和非抗生素的方式将成功地消除中耳细菌， 有助于预防复发性和慢性感染。 不仅需要挑战传统的药物治疗，而且需要开发非传统的药物治疗。 管理方法也是如此。口服抗生素治疗中耳炎的常规方法 暴露其他器官的治疗，以及中耳。局部治疗将是理想的，因为它 将限制对中耳的治疗，并为中耳提供更高浓度的药物 感染区。而且因为治疗是作为滴耳剂施用的，所以它可以在诊断时应用， 从而确保合规性。 像皮肤一样，鼓膜对大多数物质是不可渗透的，因此需要穿透 增强车辆。已经研究了其中一些，但成功有限。我们使用的是 已经被很好地描述的渗透增强车辆。它已被证明可以通过表皮， 皮肤通过毛孔形成，因此应该很可能通过鼓膜的表皮。而且是 对内耳的感觉神经结构无耳毒性。 中耳炎是世界范围内的健康问题，具有广泛的医学和社会经济挑战。 我们已经设计了一种药物，旨在更有效地消除细菌从中耳急性 中耳炎，预防复发和慢性感染。我们也在调查它的专题 经鼓膜给药与渗透增强载体，其是一种具有潜在的 用于治疗中耳炎和其它耳部疾病。