Aerosol Therapy for Lung Cancer

描述（由申请人提供）：全球每年有超过130万人死于肺癌。目前使用的传统口服和静脉化疗除了对肺外，对许多器官都有毒性作用。因此，在治疗肺癌时，剂量是有限的，通常是无效的。耐药性也减少了化疗对肺部的影响。动物研究表明，以吸入气雾剂的形式直接进入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。在这些研究中发现，吸入的化疗药物纳米颗粒（如紫杉醇、喜树碱）留在肺部的浓度比血液中的浓度高30倍。此外，5%的二氧化碳浓度的空气可以导致肺部沉积增加5.7倍，从相同的气溶胶大小和浓度。提出的技术是唯一的吸入化疗系统，结合了小气溶胶颗粒输送和CO2富集。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（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。在第一阶段的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，证明了所产生的气雾剂在最有效治疗肺癌的尺寸范围内，并表明雾化药物在体外保持其活性。新的抗癌药物制剂（拓扑替康、紫杉醇、泰索帝、依托泊苷和琥珀酸维生素E）被开发用于新的体系。第二阶段的目标是在体外和体内证明新药配方的潜在效率，并开发适用于临床前测试、临床试验和患者护理的气溶胶设备。

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.