Inhaled Large Porous Particles for Treatment of MDR-TB

吸入大孔颗粒治疗耐多药结核病

• 批准号: 7113736
• 负责人: David A Edwards
• 金额: $ 134.78万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7113736
• 关键词: aerosols; antibiotics; biomedical equipment development; clinical biomedical equipment; cooperative study; dogs; drug delivery systems; drug design /synthesis /production; drug screening /evaluation; guinea pigs; inhalation drug administration; laboratory mouse; laboratory rat; microorganism disease chemotherapy; multidrug resistance; nonhuman therapy evaluation; particle; pharmacokinetics; toxicology; tuberculosis

DESCRIPTION (provided by applicant): We seek to develop an aerosol delivery approach to more effectively treat and improve the control over transmission and outbreak of respiratory infectious diseases, specifically tuberculosis (TB) and multi-drug resistant TB (MDR-TB). Our hypothesis is that direct, topical delivery of antibiotics to infected lungs results in relatively high local drug concentrations, which can more quickly eradicate active bacterial populations, thus sterilizing the lungs and reducing the duration of infectivity and the duration of chemotherapy necessary to achieve a durable cure in pulmonary tuberculosis relative to parenteral or oral dosing. We propose to develop and test anti-TB agents and combinations that can be administered directly to patient lungs from an inexpensive, easy-to-use inhaler suitable and appropriate for use even in resource-limited settings. The agents will be formulated into large porous particles (LPPs) whose unique physical characteristics enable highly efficient delivery of relatively large drug masses. This approach has the added advantages of being non-invasive and/ or reducing gastrointestinal and systemic side effects. Specific research aims are to develop stable, LPP formulations of key anti-TB agents, establish their efficacy in animal models of TB, complete 28-day toxicology testing, and to determine reliability in the field of an existing inhaler by challenging it harsh conditions. This work will result in the identification of lead candidate antibiotic aerosols suitable for further clinical development for the improved treatment of TB and MDR-TB. It represents a new paradigm for treating and limiting the spread (especially nosocomial transmission) of respiratory infectious diseases such as TB, severe acute respiratory syndrome (SARS), influenza, and small pox.

描述（由申请人提供）： 我们寻求开发一种气溶胶输送方法，以更有效地治疗和改善对呼吸道传染病的传播和爆发的控制，特别是结核病（TB）和多药耐药TB（MDR-TB）。我们的假设是，直接局部抗生素向感染的肺部递送会导致局部药物浓度相对较高，这可以更快地消除活跃的细菌群体，从而消毒肺并减少感染性的持续时间，并降低化学疗法的持续时间，而化学疗法的持续时间与肺肺结核相对于肉毒杆菌相对或肠胃或肠胃或肉毒或肉质量的持久疗法。我们建议开发和测试可直接从廉价，易于使用的吸入器中直接给患者肺部施用的抗TB剂和组合，即使在资源有限的设置中也适用于使用。这些代理将被配制成大的多孔颗粒（LPP），其独特的物理特性可以高效地递送相对较大的药物块。这种方法具有非侵入性和/或减少胃肠道和全身副作用的额外优势。具体的研究目的是开发关键抗TB药物的稳定的LPP配方，在TB动物模型中确立其功效，完成28天的毒理学测试，并通过挑战恶劣的条件来确定现有吸入器领域的可靠性。 这项工作将导致鉴定铅候选抗生素气溶胶，适合于改善TB和MDR-TB治疗的临床开发。它代表了一种新的范式，用于治疗和限制呼吸道传染病（例如TB，严重急性呼吸系统综合征（SARS），流感和小POX）的传播（尤其是医院传播）。