Ultrasound-Enhanced Ocular Drug Delivery

超声增强眼部药物输送

基本信息

批准号：
7915554
负责人：
Vesna Zderic
金额：
$ 17.15万
依托单位：
GEORGE WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-01 至 2012-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7915554
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

项目摘要

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）：本提案重点关注治疗性超声在改善眼部药物输送中的应用。拟议的研究将解决一个重要的临床问题，因为在眼内的治疗部位通常很难达到治疗水平的药物。角膜是眼科药物输送的主要途径，充当生物屏障，通常不到 10% 的所用药物可以渗透到眼睛的前部，而几乎不会渗透到眼睛的后部。我们之前已经证明，将兔角膜暴露于治疗性超声波下，可以将药物模拟化合物输送到眼中的量增加多达 10 倍，而角膜组织的变化却很小。我们现在提议研究可以通过超声增强药物输送来解决的临床相关问题，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超声参数，这些参数可以提供临床相关的增强药物进入眼内的输送，同时仅在眼组织中产生微小且可逆的变化。首先，我们建议开发一个理论模拟模型，该模型可以预测在各种参数（频率、强度、持续时间）应用超声波之前和之后眼部药物（不同亲水性和分子大小）的角膜渗透性和占空比）。然后，我们将开发用于药物输送的治疗超声设备，该设备将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。该实验将利用白化兔的眼睛，这是眼部药物输送的常用动物模型。超声在眼部药物递送中应用的可行性将通过使用标准方法测量穿过暴露于超声或假处理（无超声应用）的角膜的药物量来确定。治疗的安全性将通过在治疗后立即和治疗后 14 天内对超声引起的角膜结构和屏障特性变化进行眼科和组织学观察来确定。我们的长期目标是开发一种廉价、快速、微创的超声药物输送方法，可应用于门诊或医院，让药物渗透到感染/炎症的眼组织中，并在特定时间输送药物。足够的浓度来对抗细菌、真菌或病毒，防止它们造成永久性视力丧失。公共卫生相关性：严重的眼部感染/炎症通常会因角膜疤痕而导致视力丧失。我们相信，治疗性超声波可以提供一种廉价且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，该方法可以更快地治疗角膜感染/炎症，从而有可能防止眼组织的永久性损伤。