(637d) Inhalable Magnetic Nanocomposite Microparticles for Application in Lung Cancer Therapy - In Vitro Safety and Efficacy Studies

Chemotherapy results in many adverse side effects when administered systemically through oral or intravenous delivery, and the localization of this therapy can result in improved therapeutic outcomes and enhanced patient response.  When treating lung cancer, targeted pulmonary administration of chemotherapy has shown enhanced therapeutic response and reduced side effects [1, 2].  Additionally, dual administration of chemotherapy and hyperthermia can result in a synergistic effect, and the combination of hyperthermia with targeted pulmonary administration of chemotherapy poses a potential improvement on current cancer treatments [3].  In this study, the in vitro safety and efficacy of inhalable dry powders was examined on a variety of representative cell lines.  These composite powders – so-called magnetic nanocomposite microparticles (MnMs) – were formulated via dilute organic suspension advanced spray drying in closed-mode and consisted of common excipients and anti-cancer drugs intelligently combined with magnetic nanoparticles.  These powders were characterized with a variety of physicochemical techniques, and their aerodynamic performance was determined with the Next Generation Impactor (NGI).  The resulting MnMs were tested in vitro with human alveolar adenocarcinoma (A549) and human bronchioalveolar carcinoma (H358) cells.  These inhalable powders were dispersed into cell culture media and exposed to the cells for a given period of time and subsequent cytotoxicity studies and transepithelial electrical resistance (TEER) measurements were performed.  Toxicity and TEER studies showed the in vitro safety of these materials up to relevant doses.  The efficacy of two common lung cancer chemotherapeutic drugs representing two different anti-cancer drug classes, cisplatin and erlotinib, was examined before and after incorporation into these materials and, the results indicated these anti-cancer drugs retained their activity.  Additionally, the activity of these drugs in combination with hyperthermia was examined, and results suggest the potential of these MnMs as a novel treatment modality for lung cancer.

References:

[1] G.A. Otterson, M.A. Villalona-Calero, S. Sharma, M.G. Kris, A. Imondi, M. Gerber, D.A. White, M.J. Ratain, J.H. Schiller, A. Sandler, M. Kraut, S. Mani, J.R. Murren, Phase I study of inhaled doxorubicin for patients with metastatic tumors to the lungs, Clinical Cancer Research, 13 (2007) 1246-1252.

[2] G.A. Otterson, M.A. Villalona-Calero, W. Hicks, X.L. Pan, J.A. Ellerton, S.N. Gettinger, J.R. Murren, Phase I/II Study of Inhaled Doxorubicin Combined with Platinum-Based Therapy for Advanced Non-Small Cell Lung Cancer, Clinical Cancer Research, 16 (2010) 2466-2473.

[3] R.D. Issels, Hyperthermia adds to chemotherapy, European Journal of Cancer, 44 (2008) 2546-2554.