Magnetic Nanodrug Delivery Through the Mucus Layer of Air-Liquid Interface Cultured Primary Normal Human Tracheobronchial Epithelial Cells

Abstract

Superparamagnetic iron oxide (Fe3O4) and highly anisotropic barium hexaferrite (BaFe12O19) nanoparticles were coated with an anti-inflammatory drug and magnetically transported through mucus produced by primary human airway epithelial cells. Using wet planetary ball milling, dl-2-amino-3-phosphonopropionic acid-coated BaFe12O19 nano-particles (BaNPs) of 1–100 nm in diameter were prepared in water. BaNPs and conventional 20–30-nm Fe3O4 nanoparticles (FeNPs) were then encased in a polymer (PLGA) loaded with dexamethasone (Dex) and tagged for imaging. PLGA-Dex-coated BaNPs and FeNPs were characterized using dynamic light scattering (DLS), transmission electron microscopy (TEM), and superconducting quantum interference device (SQUID) magnetometry. Both PLGA-Dex-coated BaNPs and FeNPs were transferred to the surface of a ~100-μm thick mucus layer of air-liquid interface cultured primary normal human tracheobronchial epithelial (NHTE) cells. Within 30 min, the nanoparticles were pulled successfully through the mucus layer by a permanent neodymium magnet. The penetration time of the nanomedicine was monitored using confocal microscopy and tailored by varying the thickness of the PLGA-Dex coating around the particles.

Advanced Mucus Infiltrating Nanoparticles for Microbicide Delivery

“…To elucidate the mechanism behind mucus penetration of loaded drugs released from NPs, ensemble-averaged geometric mean square displacements of NPs in porcine vagina tissues were defined as a function of time for such samples as the blank NPs, NPs uncoated but loaded with Nile Red, and PCN loaded with Nile Red [20,67]. As depicted in Figure 4A, the penetration rates reflected by differences in ensemble mean square displacements were examined using a quasiexperimental design [19,68].…”

Optical Imaging of Magnetic Particle Cluster Oscillation and Rotation in Glycerol

“…Nanoparticle systems have been previously investigated for their potential in treating asthma and other lung diseases [ 4 , 5 ]. For instance, to overcome mucus clearance and guide the therapeutics through the mucus barrier, magnetic iron oxide (Fe O ) nonaparticles [ 4 ] and barium hexaferrite (BaFe ) nanoparticles [ 6 ] have been used previously. For example, barium hexaferrite nanoparticles coated with an anti-inflammatory drug were pulled by external magnetic forces through the mucosal barrier [ 6 ].…”

“…For instance, to overcome mucus clearance and guide the therapeutics through the mucus barrier, magnetic iron oxide (Fe O ) nonaparticles [ 4 ] and barium hexaferrite (BaFe ) nanoparticles [ 6 ] have been used previously. For example, barium hexaferrite nanoparticles coated with an anti-inflammatory drug were pulled by external magnetic forces through the mucosal barrier [ 6 ]. These experiments showed that barium hexaferrite nanoparticles can indeed penetrate a ∼100 m thick mucus layer in a static magnetic field gradient of 360 T/m.…”

“…However, the penetration time of barium hexaferrite nanoparticles for a 100 m thick mucus layer was up to 30 min, which is too long for this technology to be applied to drug delivery through mucus barriers. Therefore, it has been proposed that magnetic particles with the ability to physically oscillate and rotate may decrease the mucus barrier penetration time by effectively cutting through the mucus mesh [ 6 ]. The work presented here investigates the magnetic field requirements for particle rotation at given frequencies and fluid viscosities.…”

“…In other works, magnetic particles have been studied for targeting and destroying cancer cells [ 18 , 19 , 20 , 21 ]. Most in vitro studies were performed in low-viscosity fluids, which ranged from to Pa·s, such as water, model bodily fluids, cell culture fluids, or alcohol [ 6 , 7 , 9 , 11 , 12 , 17 , 18 , 22 , 23 , 24 ]. In this paper, magnetic particle oscillation and rotation was investigated in glycerol with a significantly higher viscosity, i.e., ∼1 Pa·s.…”