AEROSOL BASED NANOPARTICAL DRUG DELIVERY SYSTEM--TB

气溶胶纳米颗粒给药系统--TB

• 批准号: 6389787
• 负责人: LAWRENCE K NG
• 金额: $ 22.46万
• 依托单位: UNIVERSITY OF COLORADO DENVER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2003-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389787
• 关键词: aerosols; alveolar macrophages; disease /disorder model; drug adverse effect; guinea pigs; inhalation drug administration; isoniazid; microcapsule; microorganism disease chemotherapy; nanotechnology; nonhuman therapy evaluation; respiratory disorder chemotherapy; respiratory function; slow release drug; therapy compliance; tissue /cell culture; tuberculosis

DESCRIPTION (Verbatim from Investigator's Abstract): Tuberculosis (TB) is a communicable infectious disease caused by inhalation of tubercle bacilli, Mycobacterium tuberculosis, in airborne droplets (< 10 um in size) emitted by the coughing pulmonary patient. Upon deposition in the alveolus, the tubercle bacilli can be phagocytosed and grow within the alveolar macrophages (AMs), and be eventually released causing widespread infections in the lungs and other body sites. Despite the fact that therapies are available for controlling the vast majority of existing cases, the incidence of TB is increasing. This is because many TB patients (AIDS patients, elderly, drug abusers and the urban poor) have significant social problems, and compliance with multi-month drug therapy is frequently difficult. Further, current therapies, which require patients to take large oral doses of drugs, such as isoniazid, can often produce significant side effects. This further compounds the compliance problem. Therefore, the major objectives of this research proposal are to improve the overall treatment rate of TB by developing specific pulmonary sustained drug delivery systems that would (1) improve patient's compliance with drug therapy, (2) reduce the manifestation of associated side effects, and (3) target the therapy to AM which plays an important role in the pathogenesis of TB. These objectives will be accomplished by pursuing the following specific aims: (1) developing drug-impregnated biodegradable nanoparticles of different size, shape, loading factor, and crystallinity and to determine the effects of these parameters on the release kinetics of the model antitubercular drug, isoniazid, (2) characterizing nanoparticle interaction with alveolar macrophages, (3) determining the pulmonary disposition of inhaled nanoparticles and nanoparticle-associated drugs in vivo, (4) identifying acute and chronic effects of inhaled nanoparticles on lung function and morphology, and (5) evaluating the ability of inhaled isoniazid-impregnated nanoparticles to arrest or reverse the progression of TB in an experimental animal model. It is expected this multidisciplinary approach will provide significant advances in the treatment of TB and other airway diseases in which sustained drug release or targeting AMs would be advantageous.

描述（逐字摘自研究者摘要）：结核病（TB）是一种 由吸入结核杆菌引起的传染性疾病， 结核分枝杆菌，在空气传播的飞沫（大小< 10微米），由 咳嗽的肺病患者。沉积在肺泡中时，结节 杆菌可以被吞噬并在肺泡巨噬细胞（AM）内生长， 最终释放，导致肺部和其他器官的广泛感染， 身体部位。尽管事实上有治疗方法可以控制 在绝大多数现有病例中，结核病的发病率正在上升。这是 因为许多结核病患者（艾滋病患者、老年人、吸毒者和城市 穷人）有重大的社会问题，并遵守多个月的药物 治疗通常是困难的。此外，目前的治疗，这需要 患者服用大剂量口服药物，如异烟肼，往往可以 会产生严重的副作用这进一步加剧了 问题.因此，本研究提案的主要目标是 通过发展特异性肺结核，提高结核病的总体治疗率 持续的药物输送系统，将（1）改善患者的依从性 与药物治疗，（2）减少相关副作用的表现，和 (3)针对在发病机制中起重要作用的AM进行治疗 结核病这些目标将通过以下具体努力实现： 目的：（1）研制不同粒径的载药可生物降解纳米粒 尺寸、形状、加载因子和结晶度，并确定 这些关于模型抗结核药物释放动力学的参数， 异烟肼，（2）表征纳米颗粒与肺泡 巨噬细胞，（3）确定吸入纳米颗粒的肺处置 和纳米粒相关药物在体内，（4）识别急性和慢性 吸入纳米颗粒对肺功能和形态学的影响，以及（5） 评估吸入的异烟肼浸渍的纳米颗粒阻止 或者在实验动物模型中逆转结核病的进展。是 预计这种多学科方法将在以下方面取得重大进展 肺结核和其他呼吸道疾病的治疗， 或瞄准AM将是有利的。