BIOERODIBLE INTRAVITREAL DRUG DELIVERY SYSTEMS

生物可溶性玻璃体内给药系统

• 批准号: 2430390
• 负责人: PAUL ASHTON
• 金额: $ 22.4万
• 依托单位: TUFTS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-06-01 至 1999-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2430390
• 关键词: Macaca fascicularis; Primates; biomaterial compatibility; combination chemotherapy; dexamethasone; dosage forms; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; eye disorder chemotherapy; fluorouracil; high performance liquid chromatography; hydrolysis; laboratory rabbit; nonhuman therapy evaluation; pharmacokinetics; proliferative vitreoretinopathy; slow release drug; triamcinolone

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.

该项目的广泛长期目标是1） 可植入的，可侵蚀的药物输送系统用于治疗 增殖性玻璃体病（PVR）。 2）进一步评估Codrug 概念是实现持续治疗药物水平的手段 眼睛。 鳕鱼是由两种或多种药物共价形成的共轭物 链接在一起。 链接时，鳕鱼具有极低的溶解度 因此，Codrug的颗粒溶解非常缓慢。 一旦解决方案 但是，鳕鱼被迅速水解以再生两个或更多 活性药物。 这样的系统使持续的当地药物水平成为 无需诉诸聚合物即可控制药物释放。 具体的 目的是a）研究一系列鳕鱼的水解 类固醇曲安西龙，地塞米松和曲安西尔酮乙酰酮，5-- 氟尿嘧啶在各种pHs，血清和玻璃体中，并确定最佳 化学连接。 b）准备生物毒性，可植入，持续释放 这些鳕鱼的设备并确定其体外释放。 c） 测量兔模型中的释放和组织分布 玻璃体内植入。 d）确定这些的生物相容性 设备，e）评估这些药物对PVR的功效 兔子模型。 与医疗保健相关：Codrug概念提供了 通过生物适用 设备。 在本提案中，Codrugs将被检查为 对待PVR，在最近的一项调查中被确定为面临的主要问题 玻璃体外科医生。

项目成果

Does slow-release 5-fluorouracil and triamcinolone reduce subglottic stenosis?

缓释 5-氟尿嘧啶和曲安西龙能否减少声门下狭窄？

• DOI: 10.1016/s0194-5998(98)80006-5
• 发表时间: 1998
• 期刊: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery
• 作者: Ingrams,DR;Sukin,SW;Ashton,P;Valtonen,HJ;Pankratov,MM;Shapshay,SM
• 通讯作者: Shapshay,SM