Enhancing drug delivery to human trachea through oral airway using magnetophoretic steering of microsphere carriers composed of aggregated superparamagnetic nanoparticles and nanomedicine: A numerical study

Abstract

Magnetic drug targeting (MDT) is a drug delivery method which implements a high gradient magnetic field in order to enhance the deposition of drugs, containing magnetic materials, in a target area. In this study, we investigated drug delivery to the anterior side of human trachea by means of the MDT method. The drug delivery process was studied numerically in a realistic model of human airway and the drug deposition due to the presence of magnetic field was analyzed. The human airway model used, consists of nasal cavity, oral cavity, pharynx, larynx and trachea. A steady incompressible laminar flow regime was considered for modeling the inhalation of air into the respiratory tract. Microsphere drug particles were injected orally into the airway model. The particles were assumed to have a core-shell structure with aggregated superparamagnetic magnetite nanoparticles in the core and nanomedicine stored in the shell. A permanent magnet with a stationary magnetic field was placed near the trachea in order to enhance the particle deposition in this region. Also, a human mannequin model was employed for determining the exact location of the magnet with respect to the airway. Simulations were performed for various airflow rates, particle sizes and drug compositions in the presence and absence of the magnetic field. In addition, two different air breathing conditions were examined. Furthermore, the effects of magnetic source strength, magnetic source placement angle and gravity, as well as volume packing fraction of the aggregate core, on the drug deposition were explored. The simulation results showed marked improvement in the drug deposition in the presence of magnetic field. Finally, the appropriate conditions for the efficient application of MDT were evaluated. It was shown that the optimal drug delivery results were obtained for low airflow rates (~ 5 l/min), midsize particle diameters (~ 8 µm) and high fractions of magnetic material in the particle composition (75% volume fraction). For the optimum particle diameter, the oral inhalation was shown to lead to a more successful drug delivery relative to the oronasal inhalation. Also, increasing the strength of the magnetic source, placing the magnetic source with an angle of 0° and having the patient lie on his/her back had positive impact on the MDT outcome. Moreover, increasing the volume packing fraction improved the efficieny of drug delivery for low and moderate particle sizes (≤ 8 µm).