Aerosol Deposition

Three primary mechanisms govern the deposition of aerosols in the respiratory tract: inertial impaction, sedimentation, and diffusion (Fig. 7). Early work by Landahl and coworkers showed that both sedimentation and inertial impaction in the mouth, throat, and lungs uniquely depend on the particle aerodynamic diameter [220]. Deposition by diffusional transport is independent of particle density and limited primarily to particles with geometric diameters smaller than 0.5 mm [221].

Aerodynamic diameter is the key parameter used to determine the expected depth a particle (d > 0.5 mm) will travel into the lung prior to deposition.

Diffusion

Figure 7 Primary deposition mechanisms of inhaled particles in the respiratory tract.

Diffusion

Figure 7 Primary deposition mechanisms of inhaled particles in the respiratory tract.

The quantitative relationship for the aerodynamic diameter (da) of a particle is [222]:

y where d = geometric diameter, p = particle bulk density (g/cm3), pa = water mass density (1g/cm3), and g = shape factor = 1 for a sphere. Therefore, an aerosolized particle with a geometric diameter of 1 mm and a density of 1 g/cm3 will deposit in the respiratory tract in the same manner as a 10-mm particle with a density of 0.01 g/cm3.

Particles with aerodynamic diameters between 0.02-0.05 mm and 2-5 mm that are inhaled via the mouth are capable of efficient alveolar deposition [221,223-226] (Fig. 8). Aerodynamic diameters of 1-3 mm are appropriate for particle deposition in the alveolar region when the particles are inhaled via the nose [227]. Aerodynamic diameters between 4 and 10 mm are appropriate for deposition in the bronchial region. Finally, particles of aerodynamic diameter larger than 8 mm deposit primarily in the upper airways or mouth and throat (extrathoracic region), while a significant percentage of those less than 1 mm are exhaled [228]. Due to this region-specific deposition, particles can be targeted to various areas in the lung by engineering particle aerodynamic diameter. For example, particles with an aerodynamic diameter of approximately 4-10 mm

Figure 8 Particle deposition in the human respiratory tract as a function of particle aerodynamic diameter. (Reprinted from Ref. 226. Courtesy of Medical Physics Publishing.)

Particle Diameter, Dp, j¿m

Figure 8 Particle deposition in the human respiratory tract as a function of particle aerodynamic diameter. (Reprinted from Ref. 226. Courtesy of Medical Physics Publishing.)

may be used as therapeutic vectors for bronchial delivery to treat lung disorders such as cystic fibrosis [229-231].

A particle's shape can have a significant effect on its deposition in the airways. For example, the aerodynamic diameter of a rod-shaped particle is roughly 2-3 times that of a spherical particle with a diameter equal to the width of the rod (independent of rod length) [232,233]. Therefore, long fibers with small diameters can deposit well in the deep lung [234,235]. Deposition of rod-shaped particles often results from another mechanism called interception (235237). Interception occurs when a particle's center of mass follows an airstream in the lung but the particle still impacts a wall owing to its elongated shape. Deposition by interception is especially important in small airways, where the dimensions of the airspace are comparable to the lengths of the rods [236].

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