(221b) Development of Inhalable Iron Oxide Nanocomposites for Application in Lung Cancer Therapy

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.  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.  In this study, inhalable microparticle nanocomposite dry powders containing iron oxide nanoparticles for targeted pulmonary inhalation aerosol delivery as a dry powder inhaler (DPI) were rationally designed and successfully produced via dilute organic suspension advanced spray drying in closed-mode.  An FDA-approved pharmaceutical excipient and non-reducing sugar alcohol with mucolytic properties, D-mannitol, was used in conjunction with various loadings of Fe₃O₄ nanoparticles and the physiochemical properties of the resulting powders were characterized.  Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images showed size and spherical morphology of the particles.  The size of the particles was also obtained by statistically analyzing the SEM images using SigmaScan® software.  Energy dispersive spectroscopy (EDS) confirmed the presence of iron oxide in the composite microparticle powders.  Thermal analysis by differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD) were used to determine the solid-state phase transitions and long range order, respectively.  Thermogravimetric analysis (TGA) was used to determine the amount of Fe₃O₄ incorporated into the inhalable composite microparticle powder and the water content of the powder was quantified analytically via Karl Fisher titration.  The emitted dose, respirable dose, fine particle fraction, and mass median aerodynamic diameter of the inhalable dry powders were determined with the Next Generation Impactor (NGI) and a DPI device approved for human use.  The ability to formulate a dry powder magnetic composite could have a large impact on the scientific community due to the large interest in Fe₃O₄ for biomedical applications.