title: Preparation and characterization of novel magnetic nano-in-microparticles for site-specific pulmonary drug delivery.
abstract: We propose the use of novel inhalable nano-in-microparticles (NIMs) for site-specific pulmonary drug delivery. Conventional lung cancer therapy has failed to achieve therapeutic drug concentrations at tumor sites without causing adverse effects in healthy tissue. To increase targeted drug delivery near lung tumors, we have prepared and characterized a magnetically responsive dry powder vehicle containing doxorubicin. A suspension of lactose, doxorubicin and Fe3O4 superparamagnetic iron oxide nanoparticles (SPIONs) were spray dried. NIMs were characterized for their size and morphological properties by various techniques: dynamic light scattering (DLS) and laser diffraction (LS) to determine hydrodynamic size of the SPIONs and the NIMs, respectively; next generation cascade impactor (NGI) to determine the aerodynamic diameter and fine particle fraction (FPF); scanning (SEM) and transmission (TEM) electron microscopy to analyze particle surface morphology; electron dispersive X-ray spectroscopy (EDS) to determine iron loading in NIMs; inductively coupled plasma atomic emission spectroscopy (ICP-AES) and superconducting quantum interference device (SQUID) to determine Fe3O4 content in the microparticles; and high performance liquid chromatography (HPLC) to determine doxorubicin loading in the vehicle. NIMs deposition and retention near a magnetic field was performed using a proof-of-concept cylindrical tube to mimic the conducting airway deposition. The hydrodynamic size and zeta potential of SPIONs were 56 nm and -49 mV, respectively. The hydrodynamic and aerodynamic NIM diameters were 1.6 μm and 3.27±1.69 μm, respectively. SEM micrographs reveal spherical particles with rough surface morphology. TEM and focused ion beam-SEM micrographs corroborate the porous nature of NIMs, and surface localization of SPIONs. An in vitro tracheal mimic study demonstrates more than twice the spatial deposition and retention of NIMs, compared to a liquid suspension, in regions under the influence of a strong magnetic gradient. We report the novel formulation of an inhaled and magnetically responsive NIM drug delivery vehicle. This vehicle is capable of being loaded with one or more chemotherapeutic agents, with future translational ability to be targeted to lung tumors using an external magnetic field.
authors: Department of Pharmaceutical Sciences, College of Pharmacy, ‡Nanoscience and Microsystems Graduate Program, ∥Biomedical Sciences Graduate Program, §The University of New Mexico Cancer Center, and #Department of Biochemistry and Molecular Biology, The University of New Mexico Health Sciences Center , Albuquerque, New Mexico 87131, United States.
authors: Amber A
authors: AA
authors: McBride
authors: Dominique N
authors: DN
authors: Price
authors: Loreen R
authors: LR
authors: Lamoureux
authors: Alaa A
authors: AA
authors: Elmaoued
authors: Jose M
authors: JM
authors: Vargas
authors: Natalie L
authors: NL
authors: Adolphi
authors: Pavan
authors: P
authors: Muttil
mesh_terms: D000280:Administration, Inhalation; D016503:Drug Delivery Systems / Q000379:methods*; D005290:Ferric Compounds / Q000737:chemistry*; D008168:Lung / Q000378:metabolism; D008280:Magnetics; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D014132:Trachea / Q000378:metabolism
chemical_list: D005290:Ferric Compounds; C000499:ferric oxide