BIOERODIBLE INTRAVITREAL DRUG DELIVERY SYSTEMS

该项目广泛的长期目标是：1)开发一个 可植入、可侵蚀的药物输送系统，用于治疗 增生性玻璃体视网膜病变(PVR)。2)进一步评估辅药 概念作为一种手段，以实现持续的治疗药物水平 眼睛。辅药是由两种或两种以上药物共价形成的结合物。 联系在一起。当连接时，辅药的溶解度极低。 所以可卡因的颗粒极慢地溶解。一旦进入解决方案 然而，辅药被迅速水解以再生两种或两种以上 活性药物。这样的系统使当地持续的药物水平能够 无需借助聚合物来控制药物释放即可实现。特定的 目的是a)研究一系列辅药的水解性 类固醇曲安奈德、地塞米松和曲安奈德 氟尿嘧啶在不同PHS、血清和玻璃体中的浓度并确定最适 化学反应。B)制备可生物侵蚀、可植入、缓释的药物 这些辅药的装置，并测定它们的体外释放。c) 测定药物在兔模型中的释放和组织分布 玻璃体内植入。D)确定这些材料的生物相容性 设备，e)评估这些药物对PVR的疗效 兔子模型。与医疗保健相关：辅药概念提供了 通过可生物侵蚀将多种药物输送到眼睛的手段 设备。在本提案中，将审查辅助性药物，作为一种手段 治疗PVR，在最近的一项调查中被确定为面临的主要问题 玻璃体视网膜外科医生。

The broad long-term objectives of this project are to 1) develop an implantable, erodible drug delivery system for use in the treatment of proliferative vitreoretinopathy (PVR). 2) further evaluate the codrug concept as a means to achieve sustained therapeutic drug levels in the eye. A codrug is a conjugate formed by two or more drugs covalently linked together. When linked, codrugs have exceptionally low solubility so that pellets of codrug dissolve extremely slowly. Once in solution however the codrug is rapidly hydrolyzed to regenerate the two or more active drugs. Such a system enables sustained local drug levels to be achieved without resorting to polymers to control drug release. SPECIFIC AIMS are to a) Investigate the hydrolysis of a series of codrugs of the steroids triamcinolone, dexamethasone and triamcinolone acetonide with 5- fluorouracil in various pHs, serum and vitreous and determine the optimal chemical linkage. b) Prepare bioerodible, implantable, sustained release devices from these codrugs and determine their release in vitro. c) Measure release and tissue distribution in the rabbit model after intravitreal implantation. d) Determine the biocompatibility of these devices, e) Evaluate the efficacy of these agents against PVR in the rabbit model. RELEVANCE TO HEALTH CARE: The codrug concept offers a means to deliver a wide variety of drugs to the eye via bioerodible devices. In the present proposal codrugs will be examined as a means to treat PVR, identified in a recent survey as a major problem facing vitreoretinal surgeons.