Improved TB Drug Delivery with Novel Polymeric Carriers

利用新型聚合物载体改善结核病药物输送

• 批准号: 6937964
• 负责人: IAN M ROSENTHAL
• 金额: $ 3.02万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-06-01 至 2007-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6937964
• 关键词: Mycobacterium tuberculosis; alveolar macrophages; antitubercular agents; biodegradable product; chemical synthesis; combination chemotherapy; disease /disorder model; dosage forms; drug interactions; inhalation drug administration; intravenous administration; isoniazid; laboratory mouse; method development; microorganism disease chemotherapy; pharmacokinetics; polyethylene glycols; polymers; predoctoral investigator; pyrazinamide; rifamycins; slow release drug; tuberculosis

DESCRIPTION (provided by applicant): Effective control of tuberculosis (TB) currently requires the use of long and cumbersome chemotherapeutic regimens. In order to design effective regimens that can be administered intermittently (i.e. once-weekly or less often) by inhalation or intravenous injection, novel methods of sustained drug delivery need to be rigorously explored. Recent advances in polymeric matrix-like particulate systems can provide the foundation needed to significantly improve the delivery of antituberculosis drugs. This application proposes to first develop, micropartices encapsulating various combinations of first-line anti-TB drugs using the newly developed poly(ether-anhydride) polymer and to analyze their physicochemical properties. Following that, extensive pharmacokinetic (PK) studies will be conducted in mice to determine the optimal dosage and frequency of administration of the prepared drug-loaded microparticles. Microparticle design parameters will be optimized as indicated by PK analysis. In the final phase, the applicant will rigorously determine the efficacy of intermittent poly(ether-anhydride) microparticle-based combinations in a well-defined, highly prognostic murine model of active tuberculosis designed to mimic the treatment of human disease.

描述(由申请人提供)： 要有效控制结核病，目前需要使用冗长而繁琐的化疗方案。为了设计可以通过吸入或静脉注射间歇(即每周一次或较少)给药的有效方案，需要严格探索持续给药的新方法。聚合物基质状颗粒系统的最新进展可以为显着改善抗结核药物的输送提供所需的基础。这项应用建议首先使用新开发的聚醚-酸酐聚合物开发包裹一线抗结核病药物的各种组合的微粒子，并分析它们的物理化学性质。随后，将在小鼠身上进行广泛的药代动力学(PK)研究，以确定制备的载药微粒的最佳剂量和给药频率。PK分析表明，微粒设计参数将得到优化。在最后阶段，申请者将在一个定义明确、预后良好的活动性结核病小鼠模型中严格确定间歇性聚醚-酸酐微粒组合的疗效，该模型旨在模拟人类疾病的治疗。