INTRAVITREAL DRUG DELIVERY

该项目的长期目标是： 控制药物从玻璃体中消除的物理化学性质 和B）开发可植入的持续释放装置， 玻璃体中药物的治疗、无毒浓度， 视网膜。 具体目标是：（1）开发释放 以下模型化合物在体内以稳定速率持续2个月： 庆大霉素、更昔洛韦、氟比洛芬、地塞米松、奥曲肽和 环孢菌素A 药物颗粒将以两种不同的比例包衣， 惰性聚合物，一种（聚乙烯醇）是水可渗透的，另一种是 （乙烯乙酸乙烯酯））是不可渗透的。 药物的溶解度 并且聚合物比率将决定释放速率。 (2)植入物 将装置结膜下和玻璃体内植入兔眼。 测量稳态玻璃体和水性药物水平将使得能够 吸收率和消除率。 (3)破坏色素 上皮功能并测量对稳态药物水平的影响。 碘酸钠将通过静脉注射来杀死RPE， 对药物水平的影响将指示药物浓度的速率决定步骤。 从玻璃体吸收/消除。 (4)评价缓释 环孢素A和地塞米松治疗动物的装置 葡萄膜炎和增生性玻璃体视网膜病变（PVR）模型。 车型将 be S抗原在大鼠和兔葡萄膜炎和成纤维细胞注射中的应用 兔子做PVR 与卫生保健的相关性：每200人中就有1人 葡萄膜炎导致超过30，000例法律的失明。 PVR已经 被认为是视网膜眼科医生面临的最严重的问题。 植入式缓释环孢素（视力威胁葡萄膜炎） 地塞米松（在PVR中）可能证明是治疗的一个重大进展。 更好地理解理化性质对药物的影响 可以预期吸收进入视网膜/玻璃体并从视网膜/玻璃体中消除 以帮助设计药物和输送系统，特别是用于后部 段疾病。

The broad long-term objectives of this project are to: a) investigate physicochemical properties governing drug elimination from the vitreous and b) develop implantable sustained release devices to maintain therapeutic, non-toxic concentrations of drugs in the vitreous and retina. Specific Aims are to (1) Develop implantable devices releasing the following model compounds at a steady rate for 2 months in vivo: gentamicin, ganciclovir, flurbiprofen, dexamethasone, octreotide and cyclosporine A. Pellets of drugs will be coated in varying ratios of two inert polymers, one (polyvinyl alcohol) is water permeable and the other (ethylene vinyl acetate)) is impermeable. The solubility of the drugs and the polymer ratio will determine the release rate. (2) Implant devices subconjunctivally and intravitreally into rabbit eyes. Measurement of steady state vitreous and aqueous drug levels will enable absorption and elimination rates to be calculated. (3) Disrupt pigmented epithelial function and measure the effect on steady state drug levels. Sodium iodate will be administered intravenously to kill the RPE, and effects on drug levels will indicate the rate determining steps in drug absorption/elimination from the vitreous. (4) Evaluate sustained release devices of cyclosporine A and dexamethasone in the treatment of animal models of uveitis and proliferative vitreoretinopathy (PVR). Models will be S antigen in rat and rabbit for uveitis and fibroblast injection in the rabbit for PVR. Relevance to health care: 1 in 200 people develop uveitis which causes over 30,000 cases of legal blindness. PVR has been identified as the most serious problem faced by retinal ophthalmologists. Implantable sustained release cyclosporine (in sight threatening uveitis) and dexamethasone (in PVR) may prove a significant advance in treatment. Better understanding of the effect of physicochemical properties on drug absorption into and elimination from the retina/vitreous can be expected to aid the design of drugs and delivery systems, especially for posterior segment diseases.