Novel Nanoparticle Delivery System for Antineoplastics

新型抗肿瘤纳米颗粒输送系统

• 批准号: 6483914
• 负责人: Rajan Ramaswami
• 金额: $ 10万
• 依托单位: IMARX THERAPEUTICS, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-22 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6483914
• 关键词: antineoplastics; athymic mouse; bioengineering /biomedical engineering; cell line; dosage; dosage forms; drug adverse effect; drug delivery systems; drug design /synthesis /production; electron microscopy; experimental designs; gas chromatography; high performance liquid chromatography; method development; nanotechnology; neoplasm /cancer pharmacology; paclitaxel; pharmacokinetics; polyethylene glycols; polymers; slow release drug; technology /technique development

The project focuses on development of a nanoparticulate delivery system for therapeutic agents which are difficult to solubilize in aqueous media. The formulations are particularly aimed at establishing sustained release of anti-cancer agents such as paclitaxel. Significantly improved bioavailability of the agents and reduced toxicity are afforded through the use of non-covalently associated polymeric carriers. The composition of the formulation is optimized for criteria including size, stability and drug loading. This optimization process is performed in connection with animal studies to establish toxicity and efficacy of the newly formulated drug in rodents. The pharmacokinetics of distribution of the therapeutic agent and its carriers is also investigated with the aim of optimizing the circulatory lifetime of the active agents. PROPOSED COMMERCIAL APPLICATIONS: Current estimates put the total US oncology drug market alone at $12 billion, and projected estimates of up to $25 billion in five years appear justified given the nation's aging demographics. Bristol-Myers Squibb's Taxol is a potent anti-cancer drug which posted worldwide sales of over $650 Million in the first half of 1999. Despite its potential to treat a variety of solid tumors, Taxol's use is limited due to toxic side effects. A product with the proven characteristics of paclitaxel combined with reduced toxicity and improved efficacy would be welcomed by the oncology community and gain a significant market share.

该项目的重点是开发一种纳米颗粒输送系统，用于难以溶解在水性介质中的治疗剂。所述制剂特别旨在建立抗癌剂如紫杉醇的持续释放。通过使用非共价缔合的聚合物载体，提供了显著改善的药剂生物利用度和降低的毒性。针对包括尺寸、稳定性和载药量在内的标准优化制剂的组成。该优化工艺与动物研究结合进行，以确定新配制药物在啮齿动物中的毒性和疗效。还研究了治疗剂及其载体的分布的药代动力学，目的是优化活性剂的循环寿命。拟议的商业应用：目前的估计仅美国肿瘤药物市场总额就达到120亿美元，考虑到美国人口老龄化的情况，预计五年内将达到250亿美元。百时美施贵宝公司的紫杉醇是一种强效抗癌药物，1999年上半年全球销售额超过6.5亿美元。尽管它有治疗各种实体瘤的潜力，但由于毒副作用，紫杉醇的使用受到限制。一种具有紫杉醇经证实的特性，并结合降低的毒性和改善的疗效的产品将受到肿瘤学界的欢迎，并获得显著的市场份额。