Treatment of NTM Respiratory Infections with Inhaled Drug Delivery

吸入给药治疗 NTM 呼吸道感染

• 批准号: 9347149
• 负责人: Brian N Hansen
• 金额: $ 30万
• 依托单位: AEROPHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-02-06 至 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9347149
• 关键词: Adverse effects; Aerosols; Alveolar; Amikacin; Antibiotic Therapy; Antibiotics; Beclomethasone; Breathing; Caliber; Clarithromycin; Complex; Contracts; Cutaneous; Data; Deposition; Development; Devices; Disease; Dose; Drug Delivery Systems; Drug Formulations; Fishes; Formulation; Genus Mycobacterium; Goals; Graph; Hawaii; High Prevalence; Hydrophobicity; Infection; Inhalators; Injection of therapeutic agent; Lung; Lung diseases; Macrolides; Mandatory Reporting; Medical Device; Medicine; Metered Dose Inhaler Device; Methods; Multiple drug resistant Mycobacteria Tuberculosis; Mycobacterium avium; National Institute of Allergy and Infectious Disease; Nebulizer; Oral; Organ; Pharmaceutical Preparations; Prevalence; Pulmonary Tuberculosis; Resistance; Respiratory Tract Infections; Site; Small Business Innovation Research Grant; Solubility; Source; Swimming Pools; Technology; Testing; Time; Toxic effect; Water; Woman; Work; base; cost; effective therapy; efficacy study; human old age (65+); in vivo; innovation; interest; meetings; mouse model; mycobacterial; non-tuberculosis mycobacteria; novel therapeutics; pressure; propellant; respiratory; stratospheric ozone; submicron; systemic toxicity; tuberculosis treatment

Project Summary/Abstract (Description) Significance: Non-tuberculous mycobacteria (NTM) respiratory infections is increasing across the globe. In the US, in those over 65 years-old, annual prevalence of pulmonary NTM disease increased significantly from 20 to 47 cases/100,000 between 1997-2007 with Hawaii having the highest prevalence at 396 cases/100,000. Pulmonary NTM is 1.4 times more common in women. These numbers are likely underestimated because of a lack of mandatory reporting in the U.S. Treatment of non-tuberculous mycobacterial lung disease is challenging for several reasons including the relative resistance to currently available drugs and the difficulty in tolerating prolonged treatment with multiple drugs. The only oral drugs with reliable activity against M. abscessus complex an NTM are the macrolides and clofazimine. Similar to that for M. avium complex, clofazimine was found to synergize with clarithromycin or amikacin against M. abscessus Clofazimine is an attractive agent for treatment of NTM respiratory infections including M. abscessus but cutaneous and internal organ accumulation from high oral doses cause significant toxicity. High oral doses are required to reach effective concentrations in the lungs. Inhaled doses of clofazimine have the potential to reach immediate treatment concentrations in the lungs with inhaled low doses that do not have significant systemic toxicity. Preliminary Data: Aerophase has recently demonstrated that innovative aerosol formulations of clofazimine with a new type of aerosol drug inhaler can treat TB respiratory infections without side effects from systemic toxicity. The new clofazimine formulation and aerosol device has demonstrated sustained pulmonary treatment concentration and an aerosol size range that can target the entire lung with clofazimine even alveolar regions. The Aerophase inhaled aerosol delivery method holds great promise to mitigate toxicity and allow for safe clofazimine administration directly targeted to the site of infection. Specific Aims: The first aim of this project is to treat NTM respiratory infections with inhaled clofazimine much more effectively than oral clofazimine with much lower inhaled dose. The second aim is to develop a small pocket sized metered dose inhaler with drug formulation, aerosol size, and dose optimized to treat NTM respiratory infections. The third aim will test in-vivo efficacy of inhaled clofazimine in combination with other drugs.

项目摘要/摘要（描述）