Ultrasound-Enhanced Ocular Drug Delivery

超声增强眼部药物输送

• 批准号: 7531577
• 负责人: Vesna Zderic
• 金额: $ 19.96万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7531577
• 关键词: Address; Aftercare; Ambulatory Care Facilities; Animal Model; Animals; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotics; Aqueous Humor; Back; Bacteria; Biological; Blindness; Blood; Cells; Cerebral Ischemia; Cicatrix; Clinical; Collaborations; Cornea; Development; Devices; Diffusion; Drug Delivery Systems; Eye; Eye Infections; Frequencies; Goals; Healed; Heart Arrest; Hospitals; In Vitro; Infection; Inflammation; Lead; Measurement; Mechanics; Methods; Minor; Ophthalmology; Oryctolagus cuniculus; Painless; Penetration; Permeability; Pharmaceutical Preparations; Placebos; Production; Property; Pulmonary Edema; Recovery; Research; Retina; Risk; Route; Safety; Sampling; Severities; Structure; Surface; Techniques; Testing; Therapeutic; Therapeutic Effect; Time; Tissues; Topical application; Ultrasonography; Universities; Uveitis; Virus; Vision; Washington; Work; anterior chamber; clinically relevant; clinically significant; corneal scar; fighting; fungus; healing; hydrophilicity; improved; in vivo; in vivo Model; light microscopy; liver metabolism; medical schools; minimally invasive; models and simulation; molecular size; ophthalmic drug; prevent; public health relevance; research study; treatment site

DESCRIPTION (provided by applicant): This proposal focuses on the application of therapeutic ultrasound in improving ocular drug delivery. The proposed research will address an important clinical problem since it is often difficult to achieve therapeutic levels of drugs at the treatment sites inside the eye. Cornea, which is a dominant route for delivery of ophthalmic drugs, acts as a biological barrier and usually less than 10% of the applied drug can penetrate into the front of the eye with virtually no penetration into the back of the eye. We have previously shown that exposing rabbit cornea to therapeutic ultrasound can lead to up to 10 times more delivery of a drug-mimicking compound into the eye, with only minimal changes in the corneal tissues. We are now proposing to work on clinically relevant problems that can be addressed with ultrasound-enhanced drug delivery, such as promoting delivery of antibiotics and anti-inflammatory drugs for treatment of eye infections and inflammations. Our main objective is to find ultrasound parameters that can provide clinically relevant enhancement of the delivery of medications into the eye, while producing only minor and reversible changes in the eye tissues. First, we are proposing to work on the development of a theoretical simulation model which can predict the permeability of the cornea for ocular medications (of different hydrophilicity and molecular size), before and after application of ultrasound at various parameters (frequency, intensity, duration, and duty cycle). We will then develop therapeutic ultrasound devices for drug delivery that will allow complete control of different ultrasound parameters. These devices will be tested in in-vitro and in-vivo experiments. The experiments will utilize eyes of albino rabbits, which are a usual animal model for ocular drug delivery. Feasibility of ultrasound application in ocular drug delivery will be determined by using standard methods for measurement of the amounts of drug that crosses the cornea which is exposed to ultrasound or sham-treated (no ultrasound application). Safety of the treatment will be determined by using ophthalmic and histological observations of ultrasound-induced changes in the corneal structure and barrier properties, immediately after the treatment and up to 14 days after the treatment. Our long-term goal is to develop an inexpensive, fast and minimally-invasive ultrasound method for drug delivery that can be applied in an outpatient clinic or in the hospital to allow medications to penetrate into eye tissues with infection/inflammation and deliver the drugs at a sufficient concentration to fight bacteria, fungi or viruses before they produce a permanent loss in vision. Public Health Relevance: Major eye infections/inflammations often result in the loss of vision due to corneal scarring. We believe that therapeutic ultrasound can offer an inexpensive and relatively simple method for improved delivery of medications into the eye. This method may allow faster treatment of corneal infections/inflammations as compared to currently used methods, thus potentially preventing permanent damage of the eye tissues.

描述(由申请人提供)：本提案侧重于治疗性超声波在改善眼部药物输送方面的应用。拟议的研究将解决一个重要的临床问题，因为在眼睛内的治疗部位往往很难达到治疗水平的药物。角膜是眼科药物的主要输送途径，起着生物屏障的作用，通常只有不到10%的应用药物可以穿透到眼睛的前面，而几乎没有穿透到眼睛的后面。我们之前已经证明，将兔角膜暴露在治疗性超声波下，可以导致仿药化合物进入眼睛的量增加10倍，而角膜组织只有很小的变化。我们现在提议致力于临床相关的问题，这些问题可以通过超声波增强的药物输送来解决，例如促进抗生素和抗炎药物的输送，以治疗眼部感染和炎症。我们的主要目标是找到能够在临床上增强药物进入眼内的相关超声参数，同时只在眼组织中产生轻微和可逆的改变。首先，我们建议开发一个理论模拟模型，该模型可以在不同参数(频率、强度、持续时间和占空比)下预测眼部药物(不同亲水性和分子大小)在超声作用前后的角膜渗透性。然后，我们将开发用于药物输送的治疗性超声设备，允许完全控制不同的超声参数。这些设备将在体外和体内实验中进行测试。这些实验将利用白化兔的眼睛，这是一种常见的眼部给药动物模型。超声应用于眼部药物输送的可行性将通过使用标准方法测量暴露于超声或假治疗(无超声应用)的穿过角膜的药物的量来确定。治疗的安全性将通过对超声波引起的角膜结构和屏障特性变化的眼科和组织学观察，在治疗后立即和治疗后长达14天来确定。我们的长期目标是开发一种廉价、快速和微创的药物输送方法，可应用于门诊或医院，使药物能够渗透到感染/炎症的眼组织，并在细菌、真菌或病毒造成永久性视力丧失之前以足够的浓度输送药物。 与公共卫生相关：严重的眼部感染/炎症通常会导致由于角膜疤痕造成的视力丧失。我们相信，治疗性超声波可以提供一种廉价和相对简单的方法来改善药物进入眼睛的输送。与目前使用的方法相比，这种方法可以更快地治疗角膜感染/炎症，从而潜在地防止眼睛组织的永久性损害。