Aerosol Therapy for Lung Cancer

肺癌气雾疗法

• 批准号: 7159527
• 负责人: Brian N Hansen
• 金额: $ 40.42万
• 依托单位: AEROPHASE, INC.
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-03 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7159527
• 关键词: aerosols; birth; chemotherapy; inhalation drug administration; lung; neoplasm /cancer

DESCRIPTION (provided by applicant): Lung cancer kills over 1.3 million per year worldwide. Conventional oral and i.v. chemotherapies used today have toxic effects in many organs besides the lungs. Consequently, doses are limited when treating lung cancer to an extent that it is often not effective. Drug resistance also reduces the impact of chemotherapy on the lungs. Animal studies demonstrate that anticancer drugs delivered directly to the lungs as inhaled aerosols may be the best way to treat lung cancer and other forms of cancer. In these studies it has been found that inhaled nanoparticles of chemotherapy drugs (e.g., paclitaxel, camptothecine) remain in the lungs at concentrations 30 times higher than in the blood. Furthermore, 5% CO2-enriched air can cause a 5.7-fold increase in lung deposition from the same aerosol size and concentration. The proposed technology is the only inhalation chemotherapy system that combines small aerosol particle delivery with CO2 enrichment. The aerosol-generation system is based on a patented method that uses carbon dioxide for the drug formulation and propellant. This makes it ideally suited to deliver many of the hydrophobic (non-water soluble) drugs that are easy to formulate in CO2 and difficult to formulate with water nebulizers. In the Phase I SBIR project we developed an aerosol-delivery system specifically for lung cancer treatment, demonstrated that the aerosols generated are in the size range that would be most effective for lung cancer treatment, and showed that the aerosolized drugs retained their activity in vitro. New formulations of anticancer drugs (topotecan, paclitaxel, taxotere, etoposide and vitamine E succinate) were developed for the new system. The Phase II goal is to demonstrate the potential efficiency of the new drug formulations in vitro and in vivo and to develop aerosol equipment that is suitable for pre-clinical testing, clinical trials, and patient care.

描述（由申请人提供）：全世界每年有超过 130 万人死于肺癌。传统口服和静脉注射当今使用的化疗对除肺部以外的许多器官都有毒性作用。因此，治疗肺癌时的剂量受到限制，以至于通常无效。耐药性还可以减少化疗对肺部的影响。动物研究表明，以吸入气雾剂的形式直接输送到肺部的抗癌药物可能是治疗肺癌和其他形式癌症的最佳方法。这些研究发现，吸入的化疗药物（例如紫杉醇、喜树碱）纳米粒子在肺部的残留浓度比血液中高 30 倍。此外，相同气溶胶大小和浓度的情况下，富含 5% CO2 的空气可导致肺部沉积增加 5.7 倍。所提出的技术是唯一将小气溶胶颗粒输送与二氧化碳富集相结合的吸入化疗系统。气雾剂生成系统基于一种专利方法，该方法使用二氧化碳作为药物配方和推进剂。这使得它非常适合输送许多疏水性（非水溶性）药物，这些药物很容易在二氧化碳中配制，而很难用水雾化器配制。在第一期SBIR项目中，我们开发了一种专门用于肺癌治疗的气雾剂输送系统，证明所产生的气雾剂的尺寸范围对肺癌治疗最有效，并表明雾化药物在体外保留了其活性。为新系统开发了抗癌药物的新剂型（托泊替康、紫杉醇、泰索帝、依托泊苷和维生素E琥珀酸酯）。第二阶段的目标是证明新药物制剂在体外和体内的潜在功效，并开发适用于临床前测试、临床试验和患者护理的气雾剂设备。