Methods & Noninvasive PK Study to Improve Iontophoresis

现有的治疗后眼疾病的方法是玻璃体内和眼周注射或全身给药。后眼疾病，如后葡萄膜炎、眼内炎和老年性黄斑变性，每年在美国影响超过100万人。由于后眼疾病的全身性毒性，通常不建议采用全身性给药治疗。与全身给药相比，玻璃体内和眼周注射是治疗后眼疾病更有效的给药途径，但反复注射会引起诸如疼痛、眼内出血、感染机会增加和视网膜脱离可能性等副作用。眼部注射也涉及到很高的医疗费用，因为有经验的眼科医生参与进行治疗。一种有效、低成本、稳健、无创的治疗后眼疾病的药物输送系统尚未开发。眼部给药的人体药代动力学数据也普遍缺乏。眼离子导入是一种非侵入性方法，具有将药物输送到眼后的潜力。然而，眼离子透入的机制尚不清楚，从离子传递的物理化学和工程角度来看，眼离子透入药物递送还有很大的改进空间。此外，开发一种非侵入性的方法来研究眼部药物在眼后的药代动力学将有利于眼部药物给药研究。本项目的主要目标是：(a)表征眼部离子导入的运输特性，并开发一种更有效的离子导入治疗后眼疾病的方法；(b)开发用于眼部药代动力学研究的磁共振成像（MRI），并在眼部药物输送（如离子导入）后进行这些研究。该项目将由制药和药物化学（S.K. Li，药学院，犹他大学），物理和放射学(E-K。Jeong，犹他州高级成像研究中心)和眼科学（P.S. Bernstein，莫兰眼科中心）。在本提案中获得的信息将提供一个知识库，使制药科学家能够改进眼离子导入和其他药物输送系统。如果一种有效的药物输送系统，如眼离子导入，可以取代注射和全身给药，将药物输送到眼后，这将是公众的巨大利益。

The existing methods to treat posterior eye diseases are intravitreal and periocular injections or systemic drug administration. Posterior eye diseases such as posterior uveitis, endophthalmitis, and age-related macular degeneration affect more than a million people in the United States each year. Systemic administration for the treatments of posterior eye diseases is usually not preferred because of the systemic toxicity encountered. Intravitreal and periocular injections are more effective routes of administration to treat posterior eye diseases compared with systemic drug delivery, but repeated injections cause side effects such as pain, intraocular bleeding, increased chances for infection, and the possibility of retinal detachment. Ocular injections also involve high health care cost because of the participation of experienced ophthalmologists in carrying out the treatments. An effective low-cost robust non-invasive drug delivery system for the treatments of posterior eye diseases has yet to be developed. There is also a lack of human pharmacokinetic data of ocular drug delivery in general. Ocular iontophoresis is a noninvasive method and has potential for drug delivery to the posterior of the eye. However, the mechanisms of ocular iontophoresis are not well understood, and there is much room for significant improvement of ocular iontophoretic drug delivery from the standpoint of the physical chemistry of ion transport and engineering. Also, the development of a non-invasive approach to study ocular drug pharmacokinetics in the posterior of the eye will be beneficial in ocular drug delivery research. The main objectives of the present project are (a) to characterize the transport properties of ocular iontophoresis and develop a more effective iontophoresis method for the treatment of posterior eye disease and (b) to develop magnetic resonance imaging (MRI) for ocular pharmacokinetic studies and perform these studies following ocular drug delivery such as iontophoresis. The project will be led by scientists in pharmaceutics and pharmaceutical chemistry (S.K. Li, College of Pharmacy, University of Utah), physics and radiology (E-K. Jeong, Utah Center for Advanced Imaging Research) and ophthalmology (P.S. Bernstein, Moran Eye Center). The information obtained in the present proposal will provide a knowledge base that allows pharmaceutical scientists to improve ocular iontophoresis and other drug delivery systems. It will be a great benefit to the public if an effective drug delivery system such as ocular iontophoresis can replace injections and systemic administration for drug delivery to the back of the eye.