In Silico Optimization of Fiber-Shaped Aerosols in Inhalation Therapy for Augmented Targeting and Deposition across the Respiratory Tract

Motivated by a desire to uncover new opportunities for designing the size and shape of fiber-shaped aerosols towards improved pulmonary drug delivery deposition outcomes, we explore the transport and deposition characteristics of fibers under physiologically inspired inhalation conditions in silico, mimicking a dry powder inhaler (DPI) maneuver in adult lung models. Here, using computational fluid dynamics (CFD) simulations, we resolve the transient translational and rotational motion of inhaled micron-sized ellipsoid particles under the influence of aerodynamic (i.e., drag, lift) and gravitational forces in a respiratory tract model spanning the first seven bifurcating generations (i.e., from the mouth to upper airways), coupled to a more distal airway model representing nine generations of the mid-bronchial tree. Aerosol deposition efficiencies are quantified as a function of the equivalent diameter (d(p)) and geometrical aspect ratio (AR), and these are compared to outcomes with traditional spherical particles of equivalent mass. Our results help elucidate how deposition patterns are intimately coupled to d(p) and AR, whereby high AR fibers in the narrow range of d(p) = 6–7 µm yield the highest deposition efficiency for targeting the upper- and mid-bronchi, whereas fibers in the range of d(p)= 4–6 µm are anticipated to cross through the conducting regions and reach the deeper lung regions. Our efforts underscore previously uncovered opportunities to design the shape and size of fiber-like aerosols towards targeted pulmonary drug delivery with increased deposition efficiencies, in particular by leveraging their large payloads for deep lung deposition.