Through an airway, and therefore also parallel to airway walls accordingly, alignment with a magnetic field to any other As discussed above, elongated particles have a natural tendency to align parallel to the direction of flow Drug particles may be made magnetically responsive by loading them with magnetic nanoparticles (Martin & We have previously proposed that small airway deposition of high aspect ratio particles due to interception mightīe increased through alignment of these particles with an externally applied magnetic field (Martin & Finlay, 2008a,Ģ008b). Orientation, the particle is predominantly aligned with its major axis parallel to the flow direction, and to airway walls. Velocity of the particle is not constant over a single rotation rather, a maximum occurs when the particle’s major axis isĪligned perpendicular to the flow direction, and a minimum when this axis is parallel to the flow. In their general nature, for flow parameters within the range of those found in the lung (Harris, 1972). These predictions have been validated experimentally, at least Periodically, or tumble, in shear flow (Jeffrey, 1922). It has been predicted analytically that the tendency of solid, elongated particles is to rotate In shear flow to align with their longer axes parallel to airway walls, thereby reducing the likelihood that they willĭeposit by interception. The strength of such an argument is, to a certain extent, limited by the tendency of elongated particles entrained That reduce their deposition in the upper airways as compared to mass equivalent spherical particles (Chan & Gonda,ġ989 Crowder, Rosati, Schroeter, Hickey, & Martonen, 2002 Johnson & Martonen, 1994), interception is expected toĮnhance their deposition in smaller, peripheral airways (Chan & Gonda, 1989). Whereas these particles exhibit aerodynamic propertiesĠ021-8502/$ - see front matter 䉷 2008 Elsevier Ltd. Accordingly, Chan and Gonda (1989) have previously noted that high aspect ratio drug particlesĪre well suited for targeted drug delivery to the peripheral lung. Regions of the lung, for a given particle length the interception mechanism will become increasingly significant movingĭeeper into the lung. Given thatĪirway diameters decrease by almost two orders of magnitude between the trachea and the peripheral, gas-exchange Through an airway (Balashazy, Martonen, & Hofmann, 1990 Cai & Yu, 1988 Myojo & Takaya, 2001). Deposition by interceptionĭepends on the ratio between particle length and airway diameter, as well as on the orientation of a particle as it travels Taken into account, this being the interception of the tip of a particle with an airway wall. In considering the inhalation of elongated, high aspect ratio particles, an additional deposition mechanism must be Well as on the airway geometry and flow patterns within that region (Finlay, 2001 ICRP, 1994).
Tract, the probability of deposition due to the three primary mechanisms is dependant on particle size and density, as Other deposition mechanisms can become important (e.g. (Coates, 2008 Finlay, 2001 Heyer & Svartengren, 2002 Martonen & Yang, 1996), though under special circumstances Primarily occurs through inertial impaction, gravitational sedimentation, or Brownian diffusion onto airway walls For compact, approximately spherical, aerosol particles, deposition In determining drug dosages delivered to the lung. Respiratory tract deposition of inhaled pharmaceutical aerosols has been studied extensively due to its importance Keywords: Aerosol drug delivery Magnetic drug targeting Aerosol deposition Magnetic nanoparticles Inhalation This approach shows promise for targeting aerosolĭrug delivery to specific locations within the lung. Unlike previousĪpproaches to magnetic drug targeting, the approach presented herein requires no gradient in the magnetic field strength, and can beĪccomplished with small amounts of magnetic material compared to active drug. Enhanced deposition ofĪligned particles is measured in vitro in a physical model of the small, bifurcating airways found in the lung. Loaded with magnetic nanoparticles by controlling particle orientations through magnetic field alignment. The present work describes a new approach for non-invasively targeting respiratory tract deposition of high aspect ratio aerosols Received 17 January 2008 received in revised form 3 April 2008 accepted 4 April 2008 Enhanced deposition of high aspect ratio aerosols in small airwayīifurcations using magnetic field alignmentĭepartment of Mechanical Engineering, University of Alberta, Edmonton, Alberta, Canada T6G 2G8
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