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.

中耳炎是一种全球疾病，主要影响5岁以下的儿科人群。它 是小儿护理就诊和抗生素治疗的最常见原因。过度的处方和差 - 合规性导致细菌对抗生素的敏感性降低了，因此，复发性和 慢性耳病。显然，有必要研究替代性治疗方式。 中耳是一个大腔。它利用了对陷阱的先天免疫反应的组件 细菌，含有吞噬细胞消除它们。但是，这些组件也可以封装 细菌并通过免疫逃避保护它们。 我们将调查公式对治疗既有先天介质的治疗中耳炎的疗效 中耳对感染和病原体的反应。我们首先将细菌的宿主遏制靶向 暴露于治疗。治疗包括有效的抗菌肽和早期的关键分子 中耳粘膜对感染的先天反应。细菌也将用 抗生素/皮质类固醇。细菌耐药性是全球健康问题。我们相信我们的组合 抗生素和非抗生素方式将成功地消除中耳细菌 有助于防止复发和慢性感染。 不仅有必要挑战传统的药物治疗，而且需要发展非传统的药物治疗 也是管理方法。用口服抗生素治疗中耳炎的常规方法 暴露其他器官以及中耳。主题治疗将是理想的选择 将限制中耳的治疗，并提供更高的药理剂 感染区域。而且由于治疗是作为耳朵滴管的，因此可以在诊断时应用 从而确保合规。 像皮肤一样，鼓膜膜对大多数物质都不渗透，因此需要穿透 增强工具。其中许多已经进行了研究，但成功率有限。我们正在使用 渗透性增强车的特征是。已经证明它可以通过 皮肤通过孔形成，因此可能会通过鼓膜膜的表皮。而且，是 对内耳的感觉神经结构不是耳毒性。 中耳炎媒体是世界范围内的健康问题，面临广泛的医疗和社会经济挑战。 我们设计了一种药物，旨在更有效地从急性中的中耳中消除细菌 中耳炎的阶段，防止复发和慢性感染。我们同样正在调查其主题 具有渗透性增强载体的倍跨性给药，具有强大的溶剂 用于治疗中耳炎和其他耳部疾病。