AEROSOL BASED NANOPARTICAL DRUG DELIVERY SYSTEM--TB

气溶胶纳米颗粒给药系统--TB

• 批准号: 6537355
• 负责人: LAWRENCE K NG
• 金额: $ 16.63万
• 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 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6537355
• 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（摘自研究者摘要）：结核病（TB）是一种疾病

项目成果

Quantification of isoniazid and acetylisoniazid in rat plasma and alveolar macrophages by liquid chromatography-tandem mass spectrometry with on-line extraction.

采用在线萃取液相色谱-串联质谱法定量大鼠血浆和肺泡巨噬细胞中的异烟肼和乙酰异烟肼。

• DOI: 10.1016/j.jchromb.2006.10.008
• 发表时间: 2007
• 期刊: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences
• 作者: Ng,Ka-yun;Zhou,Huiyu;Zhang,YanLing;Hybertson,Brooks;Randolph,Theodore;Christians,Uwe
• 通讯作者: Christians,Uwe

Microparticle-based lung delivery of INH decreases INH metabolism and targets alveolar macrophages.

基于微粒的 INH 肺部递送可降低 INH 代谢并靶向肺泡巨噬细胞。

• DOI: 10.1016/j.jconrel.2005.06.009
• 发表时间: 2005
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Zhou,Huiyu;Zhang,Yanling;Biggs,DanielleL;Manning,MarkC;Randolph,TheodoreW;Christians,Uwe;Hybertson,BrooksM;Ng,Ka-yun
• 通讯作者: Ng,Ka-yun