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Improved Method of Drug Delivery to the Inner Ear

内耳药物输送的改进方法

基本信息

批准号：
8088089
负责人：
Kevin S. Li
金额：
$ 18.86万
依托单位：
UNIVERSITY OF CINCINNATI
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-15 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8088089
关键词：
Adrenal Cortex Hormones Adverse effects Adverse event Animal Model Animals Body Surface Body Temperature Catheters Cells Chemicals Chronic Cidofovir Complex Deposition Development Dexamethasone Diffusion Distal Dose Drug Controls Drug Delivery Systems Electrodes Eustachian Tube Evaluation External Ear External auditory canal Gel Goals Health Care Costs Hearing problem Hydrogels In Vitro Infusion Pumps Injection of therapeutic agent Iontophoresis Kinetics Knowledge Labyrinth Lead Liquid substance Literature Mechanics Membrane Metabolic Clearance Rate Methods Modeling Molecular Needles Pharmaceutical Preparations Phase Transition Polymers Pump Risk Solutions Source Structure System Systems Development Technology Temperature Therapeutic Agents Time Toxic effect Transition Temperature Tympanic membrane base copolymer drug clearance drug discovery effective therapy electric field hearing impairment implant coating improved in vivo in vivo Model inner ear diseases middle ear novel ototoxicity physical property public health relevance residence round window

项目摘要

DESCRIPTION (provided by applicant): The existing methods of drug delivery to the inner ear such as the deposition of therapeutic agents in the middle ear on the round window membrane (RWM) by intratympanic injections are not very effective. Systemic corticosteroid therapy is also problematic due to systemic side effects. Intracochlear injections provide more precise dosing but are not long lasting that effective treatments may require multiple dosing, this increasing the risks of damaging the cochlear. Other methods of intratympanic and intracochlear delivery such as the use of catheters, pumps (e.g., osmotic pump, infusion pump), injectors, and drug coated implants are complicated due to the complex mechanics involved. Because of the challenges in inner ear drug delivery, many inner ear disorders cannot be treated effectively. With the recent advances in drug discovery of new chemical entities and new knowledge in hearing disorders, there is an unmet need to effectively deliver drugs to the inner ear. The objective of the present project is to develop a robust, long- lasting, and safe method of drug delivery to the inner ear using a sustained release temperature sensitive gel and controlled delivery using iontophoresis. A temperature sensitive gel system that is a liquid at room temperature to conform on the round window niche and solidify at body temperature will first be evaluated to provide sustained baseline inner ear delivery via the RWM. This gel will be placed in the middle ear by intratympanic injection, and has a significant advantage over the conventional intratympanic injection method. To enhance drug delivery from the gel to the inner ear on an as-needed basis, iontophoresis will be used. In addition to enhance drug delivery, iontophoresis will also be used to replenish the drug in the gel when needed over the treatment. Iontophoresis will be performed with the electrode placed in the external ear in electrical contact with the tympanic membrane, which in turn is in contact with the gel system in the middle ear, with the gel in the middle ear serves as both the drug depot and a conduit of the electric current from the electrode in the external ear to the RWM. The ultimate goal of the project is to develop a drug delivery platform for inner ear delivery that is effective and well tolerated while easy to administer. PUBLIC HEALTH RELEVANCE: There is an unmet need to develop a robust, long lasting, and safe drug delivery method for the inner ear to take advantage of the new knowledge in the treatment of hearing disorders. The present project will begin the development of a drug delivery method using a temperature sensitive hydrogel that is a solution at room temperature but gel in the middle ear for sustained drug delivery to the inner ear. Iontophoresis will then be developed that can be applied noninvasively to the external ear for controlled drug delivery from this hydrogel on an as-needed basis. It is believed that this method can allow convenient and safe treatment of inner ear diseases.

描述（由申请人提供）：现有的药物递送到内耳的方法，例如通过鼓室内注射将治疗剂沉积在中耳中的圆窗膜（RWM）上，不是非常有效。由于全身副作用，全身皮质类固醇治疗也是有问题的。耳蜗内注射提供了更精确的剂量，但持续时间不长，有效的治疗可能需要多次给药，这增加了损伤耳蜗的风险。鼓室内和颅内递送的其他方法如使用导管、泵（例如，渗透泵、输注泵）、注射器和药物涂层植入物由于涉及复杂的机械而变得复杂。由于内耳药物递送的挑战，许多内耳疾病不能得到有效治疗。随着新化学实体的药物发现和听力障碍的新知识的最新进展，有效地将药物递送到内耳的需求尚未得到满足。本项目的目的是开发一种稳健、持久和安全的药物递送至内耳的方法，该方法使用持续释放温度敏感凝胶和使用离子电渗的受控递送。将首先评价在室温下为液体以符合圆窗龛并在体温下固化的温度敏感凝胶系统，以通过RWM提供持续的基线内耳递送。这种凝胶将通过鼓室内注射放置在中耳中，并且与传统的鼓室内注射方法相比具有显著的优势。为了根据需要增强从凝胶到内耳的药物递送，将使用离子电渗疗法。除了增强药物递送外，离子电渗疗法还将用于在治疗期间需要时补充凝胶中的药物。将使用放置在外耳中与鼓膜电接触的电极进行离子电渗，鼓膜又与中耳中的凝胶系统接触，中耳中的凝胶用作药物贮库和电流从外耳中的电极到RWM的导管。该项目的最终目标是开发一种用于内耳递送的药物递送平台，该平台有效且耐受性良好，同时易于管理。公共卫生关系：开发用于内耳的稳健、持久和安全的药物递送方法以利用听力障碍治疗中的新知识的需求尚未得到满足。本项目将开始开发一种使用温度敏感性水凝胶的药物递送方法，该水凝胶在室温下是溶液，但在中耳中是凝胶，用于向内耳持续递送药物。然后将开发离子电渗疗法，其可以非侵入性地应用于外耳，以根据需要从该水凝胶控制药物递送。据信，这种方法可以方便和安全地治疗内耳疾病。