AEROSOL BASED NANOPARTICAL DRUG DELIVERY SYSTEM FOR TUBE

基于气溶胶的纳米颗粒管给药系统

• 批准号: 2842828
• 负责人: LAWRENCE K NG
• 金额: $ 25.25万
• 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/2842828
• 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 因吸入结核杆菌而引起的传染性疾病， 结核分枝杆菌，存在于空气中的飞沫（尺寸 < 10 微米）中 咳嗽的肺部病人。结节沉积在肺泡中后 杆菌可以被吞噬并在肺泡巨噬细胞（AM）内生长，并且 最终被释放，导致肺部和其他部位广泛感染 身体部位。尽管事实上有治疗方法可以控制 就现有的绝大多数病例而言，结核病的发病率正在增加。这是 因为许多结核病患者（艾滋病患者、老年人、吸毒者和城市居民） 差）有严重的社会问题，并且遵守多月药物治疗 治疗常常很困难。此外，目前的疗法需要 患者经常服用大剂量口服药物，如异烟肼 产生显着的副作用。这进一步加剧了合规性 问题。因此，本研究计划的主要目标是 通过开发特异性肺结核来提高结核病的总体治疗率 持续给药系统将 (1) 提高患者的依从性 通过药物治疗，(2) 减少相关副作用的表现，以及 (3)针对在发病机制中起重要作用的AM进行靶向治疗 结核病。这些目标将通过追求以下具体目标来实现 目标：（1）开发不同的药物浸渍的可生物降解纳米颗粒 尺寸、形状、负载因子和结晶度，并确定其影响 这些参数对模型抗结核药物的释放动力学的影响， 异烟肼，(2) 表征纳米颗粒与肺泡的相互作用 巨噬细胞，(3) 确定吸入纳米颗粒的肺部分布 和体内纳米颗粒相关药物，(4) 识别急性和慢性 吸入纳米颗粒对肺功能和形态的影响，以及（5） 评估吸入的异烟肼浸渍纳米颗粒的阻滞能力 或在实验动物模型中逆转结核病的进展。这是 预计这种多学科方法将在以下方面取得重大进展： 治疗结核病和其他需要持续药物释放的气道疾病 或瞄准 AM 将是有利的。