Federation of American Scientists Case Studies in Dual Use Biological Research Module 3.0: Aerosol Delivery Case Study
Topic: Desigining Porous Particles Subtopic: Size Matters

Recently research has turned to the aerodynamic properties of the aerosol particles by applying the principles of “Stokes Law,” which describes how the radius of a sphere and the viscosity of a fluid predict the force needed to move it without settling. To optimize drug delivery to the lungs the physical implications of particle slip, shape, and density need to be considered. The location of deposition for particles used in inhaled medicines is a function of aerodynamic diameter and density. Larger particles (> 5µm) tend to deposit in the mouth and the upper reaches of the bronchial airways, getting caught by the ciliated cells that line the upper airway much the way dust and pollen do. Moderately sized particles (between 1 and 5µm), on the other hand, tend to deposit in the central and peripheral airways and in the alveoli but are often scavenged by macrophages. Particles with an aerodynamic diameter less than 1µm remain suspended in air and are generally exhaled. Edwards and his colleagues realized that ultimately they would have to try to get drug particles that were large enough to evade macrophages past the ciliated cells of the upper respiratory tract and deep into the lungs.

Drug aerosol particle engineering often focused on designing particles with a standardized size range of 1 to 5µm to permit efficient inhalation and deposition, but Edwards chose to use particles of non-standardized density and geometric size. He posited that large porous particles would have the mass and aerodynamic properties of smaller particles but could effectively evade scavenging macrophages in the alveoli because of their size. This would reduce the frequency of dosing while ensuring deep lung penetration of medication.

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Topic History Asthma and Aerosolized Medicines Designing Porous Particles Implications Discussion References Home