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. ? ? ?