Aerosol Therapy for Lung Cancer

描述(申请人提供)：全球每年有130多万人死于肺癌。常规口服和静脉注射。今天使用的化疗药物除了对肺部有毒性作用外，还对许多器官有毒性作用。因此，在治疗肺癌时，剂量是有限的，以至于往往无效。抗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将抗癌药物输送到肺部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，已经发现吸入的化疗药物纳米粒(例如紫杉醇、喜树碱)在肺部的浓度比在血液中的浓度高30倍。此外，在相同的气溶胶大小和浓度下，5%的二氧化碳浓度可以导致肺沉积增加5.7倍。这项拟议的技术是唯一一种将小气溶胶颗粒输送与二氧化碳浓缩相结合的吸入性化疗系统。气雾剂产生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，这些药物在二氧化碳中很容易配制，而用水雾化器很难配制。在第一阶段SBIR项目中，我们开发了一种专用于肺癌治疗的气雾剂释放系统，证明了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持了它们的活性。为新系统开发了抗癌药物的新配方(拓扑替康、紫杉醇、紫杉醇、依托泊苷和维生素E琥珀酸酯)。第二阶段的目标是展示新药物制剂在体外和体内的潜在效率，并开发适合临床前测试、临床试验和患者护理的气雾剂设备。

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.