Formulation and characterization of inhalable magnetic nanocomposite microparticles (MnMs) for targeted pulmonary delivery via spray drying

Targeted pulmonary delivery facilitates the direct application of bioactive materials to the lungs in a controlled manner and provides an exciting platform for targeting magnetic nanoparticles (MNPs) to the lungs. Iron oxide MNPs remotely heat in the presence of an alternating magnetic field (AMF) providing unique opportunities for therapeutic applications such as hyperthermia. In this study, spray drying was used to formulate magnetic nanocomposite microparticles (MnMs) consisting of iron oxide MNPs and D-mannitol. The physicochemical properties of these MnMs were evaluated and the in vitro aerosol dispersion performance of the dry powders was measured by the Next Generation Impactor (R). For all powders, the mass median aerosol diameter (MMAD) was < 5 mu m and deposition patterns revealed that MnMs could deposit throughout the lungs. Heating studies with a custom AMF showed that MNPs retain excellent thermal properties after spray drying into composite dry powders, with specific absorption ratios (SAR) > 200 W/g, and in vitro studies on a human lung cell line indicated moderate cytotoxicity of these materials. These inhalable composites present a class of materials with many potential applications and pose a promising approach for thermal treatment of the lungs through targeted pulmonary administration of MNPs. (C) 2014 Elsevier B.V. All rights reserved.