CORE--DEVELOPMENT AND TESTING OF POLYMER-DRUG FORMULATIONS

核心——聚合物药物制剂的开发和测试

• 批准号: 6102630
• 负责人: CRAIG R SMITH
• 金额: --
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-07-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6102630
• 关键词: antiseptic sterilization; biomedical facility; biotransformation; camptothecin; carbohydrates; chemical stability; cis platinum compound; cooperative study; drug delivery systems; drug design /synthesis /production; drug quality /standard; drug screening /evaluation; gamma radiation; implant; medical implant science; neoplasm /cancer pharmacology; paclitaxel; polymers

The approach of this NCDDG is to continue to develop biodegradable polymers that can be implanted at the site of the tumor and release effective drugs in a controlled manner as the polymer is degraded. Other programs are concerned with research related to providing new polymers and delivery systems for anti cancer drugs. Our program is aimed at development and is designed to provide polymer-drug combinations in optimal, reproducible formulations so that they can be tested in animals (preclinical); the effective formulations will be then scaled-up and extensively studied to be appropriate for human clinical trials (beyond the scope of this proposal). Through the previous NCDDG we have established the requirements for a suitable degradable implant to the brain by using the BCNU-polymer combination as representative. During the course of bringing this device through clinical trials many chemical, pharmaceutical, and pharmacological issues were investigated and the appropriate procedures have been established. These include: scale-up and quality control procedures for polymer manufacturing and drug incorporation; toxicology of the placebo and BCNU-loaded polymer under various conditions; and new polymers and various drugs were introduced to the program. The specific aims of the current proposals are to 1) develop procedures for large scale production of clinical grade drug-polymer implants, focusing on the use of automated compression and injection molding processes, 2) develop methods to produce sufficient quantities of the new polymers and delivery systems developed,in other programs and supply of quality polymers and drug incorporated devices to the other programs, 3) Develop validated methods for the evaluation of the shelf life stability of anticancer polyanhydride delivery systems, 4) develop methods for studying Polymer-Drug interaction and protein stability in polymers, and 5) Determine the optimal gamma- irradiation sterilization dose for polyanhydride based delivery systems.

该NCDG的方法是继续发展可生物降解 可以植入肿瘤部位并释放的聚合物 当聚合物降解时，有效药物以受控方式受控。其他 计划涉及与提供新聚合物和 抗癌药物的输送系统。我们的计划针对 开发，旨在提供聚合物 - 药水组合 最佳，可再现的配方，以便可以在动物中进行测试 （临床前）;然后将有效配方缩放，并 经过广泛研究以适合人类临床试验（超越 该提议的范围）。 通过以前的NCDDG，我们已经确定了 通过使用BCNU - 聚合物，合适的降解植入物可以植入到大脑中 组合作为代表。在带上这款设备的过程中 通过临床试验，许多化学，药物和药理 研究了问题，适当的程序已经 已确立的。其中包括：扩大和质量控制程序 聚合物制造和药物掺入；安慰剂的毒理学 和BCNU负载的聚合物在各种条件下；以及新的聚合物和 该计划引入了各种药物。特定目标 当前的建议是1）开发大规模生产的程序 临床级药物聚合物植入物，重点是使用自动化 压缩和注入成型过程，2）开发产生的方法 足够数量的新聚合物和输送系统 在其他计划和质量聚合物和药物的供应中开发 将设备合并到其他程序，3）开发经过验证的方法 用于评估抗癌多醇的保质期稳定性 输送系统，4）开发研究聚合物 - 药物相互作用的方法 和聚合物中的蛋白质稳定性，以及5）确定最佳γ- 基于多丙二醇的递送系统的辐照灭菌剂量。