Aerosol Therapy for Lung Cancer

肺癌气雾疗法

• 批准号: 7255713
• 负责人: Brian N Hansen
• 金额: $ 37.11万
• 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 2010-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7255713
• 关键词: A549; Address; Aerosol Drug Therapy; Aerosol Propellants; Aerosols; Affect; Air; Animals; Antineoplastic Agents; Apoptotic; Blood; Breast; Breathing; Cancer Etiology; Cancer cell line; Carbon Dioxide; Cessation of life; Clinical; Clinical Trials; Colon Carcinoma; Data; Deposition; Devices; Disease; Distal; Dose-Limiting; Drug Delivery Systems; Drug Formulations; Drug resistance; Equipment; Ethanol; Etoposide; Etoposide/Paclitaxel; Etoposide/Topotecan; Excision; Feasibility Studies; Foundations; Future; Generations; Global Warming; Goals; Grant; Human; In Vitro; Inhalators; Legal patent; Liquid substance; Lung; Malignant Neoplasms; Malignant neoplasm of lung; Measures; Medicine; Metered Dose Inhaler Device; Methods; Moderate Exercise; Nebulizer; Non-Small-Cell Lung Carcinoma; Numbers; Operative Surgical Procedures; Oral; Organ; Paclitaxel; Paclitaxel/Topotecan; Patient Care; Personal Satisfaction; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Preclinical Testing; Prostate; Radiation; Range; Rate; Research; Site; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Solubility; Solvents; Staging; Succinates; System; Systemic Therapy; Technology; Testing; Tidal Volume; Time; Today; Toxic effect; Toxicology; United States Food and Drug Administration; Water; Woman; Work; aerosolized; aqueous; base; cancer cell; cancer therapy; cancer type; chemotherapeutic agent; chemotherapy; commercialization; cost; docetaxel; drug testing; in vivo; inhibitor/antagonist; instrument; killings; light weight; men; mortality; nanoparticle; novel; novel strategies; particle; pre-clinical; pressure; propellant; prototype; size; success; succinate; surfactant; targeted delivery; tumor; vitamin E succinate

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）：肺癌每年在全世界造成130多万人死亡。目前使用的传统口服和静脉化疗对除肺外的许多器官都有毒性作用。因此，当治疗肺癌时，剂量是有限的，以至于通常无效。耐药性也减少了化疗对肺部的影响。动物研究表明，以吸入气雾剂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。在这些研究中，已经发现化疗药物的吸入纳米颗粒（例如，紫杉醇、喜树碱）以比血液中高30倍的浓度保留在肺中。此外，5%的富CO2空气可导致相同气溶胶尺寸和浓度的肺沉积增加5.7倍。所提出的技术是唯一一种将小气雾剂颗粒输送与CO2富集相结合的吸入化疗系统。气溶胶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，这些药物易于在CO2中配制，难以用水雾化器配制。在第一阶段SBIR项目中，我们开发了一种专门用于肺癌治疗的气溶胶输送系统，证明产生的气溶胶的尺寸范围对肺癌治疗最有效，并表明雾化药物保留了其活性体外。抗癌药物（拓扑替康，紫杉醇，泰索帝，依托泊苷和维生素E琥珀酸酯）的新配方开发的新系统。第二阶段的目标是证明新药物制剂在体外和体内的潜在效率，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。