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，用于治疗难以溶于水介质的药物。该制剂特别旨在建立抗癌剂如紫杉醇的缓释。通过使用非共价结合的聚合物载体，显著提高了药物的生物利用度并降低了毒性。该制剂的组成是优化的标准，包括大小，稳定性和药物负荷。该优化过程与动物研究相结合，以确定新配制的药物在啮齿动物中的毒性和功效。还研究了药物及其载体分布的药代动力学，以优化活性药物的循环寿命。拟议的商业应用：目前估计美国肿瘤药物市场总额为120亿美元，考虑到美国人口老龄化，预计五年内将达到250亿美元，这似乎是合理的。百时美施贵宝的紫杉醇是一种有效的抗癌药物，1999年上半年全球销售额超过6.5亿美元。尽管紫杉醇有治疗多种实体肿瘤的潜力，但由于毒副作用，它的使用受到限制。一种具有紫杉醇特性且毒性降低、疗效提高的产品将受到肿瘤学界的欢迎，并获得可观的市场份额。