Directed drug delivery: inhalable magnetic nano‐in‐microparticles for the application of lung cancer

Abstract

Lung cancer, the leading cause of cancer mortality, annually kills 1.4M people. Despite advances in surgery, drug discovery and therapy, lung cancer remains a difficult disease to treat. We propose that targeted inhaled drug delivery to the respiratory tract will facilitate treatment with lower systemic exposure and consequently, reduce side effects. Novel inhalable dry powders will be directed to tumors in the lung airways by a magnetic field gradient concentrating drug at the disease site. Previous studies using inhaled chemotherapeutics showed dose limiting pulmonary toxicity due to the non‐specificity of the delivery mechanism. We believe that targeted inhaled therapies could mitigate this problem. We successfully formulated and characterized the magnetically responsive nano‐in‐microparticles (NIMs) delivery vehicle containing superparamagnetic iron oxide nanoparticles (SPIONs) and doxorubicin for site‐specific pulmonary drug delivery. NIMs were characterized for their size, morphological properties, Fe3O4 loading and drug loading. The hydrodynamic diameter and aerodynamic diameter of NIMs were 1.6 μm and 3.27± 1.69 μm, respectively. SEM images show spherical particles with rough surface morphology. We have shown the ability to direct and retain NIMs in a proof‐of‐concept tube study to mimic human conducting airways with deposition of NIMs in regions experiencing a strong magnetic gradient. We have also administered NIMs in a healthy rat model by pulmonary route to demonstrate NIMs targeting capability, and to characterize their spatial deposition in the lung in vivo. These studies could radically change treatment modalities for lung cancer patients by increasing patient survival rates as well as reducing the side effects observed with current chemotherapies.