Tumor-penetrating aerosol nanocomposite microparticles for the treatment of lung cancer

Abstract

One of the major public health problems in the Unites States is cancer, where over 1 in 4 deaths is due to this disease each year. As of 2010, lung and bronchus cancers are the leading types of cancer-related deaths in all ages for males and females in the US [1]. The chemotherapeutic treatment most often applied for lung cancer is intravenous paclitaxel (PTX) in the form of Taxol. Methods used to treat respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) involve the use of aerosols devices. The first use of aerosolized chemotherapy was reported in 1968 [2]. The advantage of using aerosols treatment is the targeting directly to the lungs and the reduction of systemic side effects provoked by high doses of drug in the body. In this project we have developed a dry powder nanocomposite microparticle (nCmP) aerosol containing PTX-loaded nanoparticles comprised of acetalated dextran (Ac-Dex). Ac-Dex is easily biodegradable and results in fast release of therapeutic agents under acidic conditions as seen in tumor tissues [3]. In addition to the drug, a tumor-penetrating peptide (iRDG) was conjugated to Ac-Dex to help the targeting and penetration into the inner layers of solid tumors. Finally, we formulated nCmPs in mannitol via spray drying. The effectiveness of the complex drug produced was tested in lung cancer cells (A459 lung adenocarcinoma) in two-dimensional (2-D) and three-dimensional (3-D) cell culture studies.