Magnetic nanodrug delivery through the mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial cells.

ORAL

Abstract

In several prominent human lung diseases, such as asthma, patients produce a thickened mucosal fluid, irritating and inflaming the underlying tissue that progresses the condition. Many current drug therapies prove ineffective due to the inability to penetrate this thickened mucosal layer. In this study, superparamagnetic Fe$_{\mathrm{3}}$O$_{\mathrm{4}}$ and highly anisotropic BaFe$_{\mathrm{12}}$O$_{\mathrm{19}}$ nanoparticles were surface-engineered for the purpose of transporting anti-mucin medicine through the mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial (NHTE) cells via magnetic field gradient. Using wet planetary ball milling, surfactant-coated BaFe$_{\mathrm{12}}$O$_{\mathrm{19}}$ nanoparticles (BaNPs) of 60 nm in diameter were prepared in water. BaNPs and conventional 30 nm surfactant-coated Fe$_{\mathrm{3}}$O$_{\mathrm{4}}$ nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging. Both PLGA-Dex coated BaNPs and FeNPs were added on top of an approximately 100 micrometer thick mucus layer of air-liquid interface cultured NHTE cells. Within 30 minutes, PLGA-Dex coated FeNPs and BaNPs were pulled successfully through the mucus layer by a permanent neodymium magnet for the first time. The penetration time of the nanomedicine was monitored using confocal microscopy.

Authors

  • Kathrin Spendier

    University of Colorado at Colorado Springs

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra

  • Scott D. Bergesen

    Santa Fe Institute, Arizona State University, Department of Physics and Center for Biological Physics, Arizona State University, Brigham Young University Department of Physics and Astronomy, Brigham Young University, Utah Valley University, Dixie State College, Advisor, Student, Massachusetts Institute of Technology, Thomas Jefferson National Accelerator Laboratory, Colorado College, United States Air Force Academy, Georgia Institute of Technology, Utah State University, Brigham Young University - Idaho, Utah State University- Logan, National Institute of Standards and Technology, Humboldt State University, UC Santa Cruz, Institut de Chimie des Substances Naturelles, Arizona State Univ, University of Colorado at Colorado Springs, National Jewish Health, Department of Physics, The University of Texas at Austin, Department of Physics, New Mexico State University, U. S. Air Force Academy, Brigham Young Univ - Provo, University of New South Wales, University of Texas, University of Warwick, University of Louisiana, Department of Physics and Astronomy, Brigham Young University, Provo, Utah 84602, USA., Center for Materials Genomics, Department of Mechanical Engineering and Materials Science and Department of Physics, Duke University, Durham, North Ca, Duke University, Durham, North Carolina., Brigham Young University -- Provo, Utah, General Atomics -- San Diego, California, Department of Mathematics, University of British Columbia, Department of Physics, Arizona State University, UC Riverside, UMASS, STScI, NOAO, UT Austin, Texas A&M, Arizona State Univeristy, New Mexico State Univ, Los Alamos National Laboratory, Colorado State Univ, Department of Physics, Oregon State University, Colorado School of Mines, University of Alaska, Fairbanks, The Peac Institute of Multiscale Modeling, UNSW Canberra