Targeting Inhaled Fibers to the Pulmonary Acinus: Opportunities for Augmented Delivery From in Silico Simulations

Eur J Pharm Sci. 2019 Sep 1;137:105003. doi: 10.1016/j.ejps.2019.105003. Epub 2019 Jul 11.

Abstract

Non-spherical particles, and fibers in particular, are potentially attractive airborne carriers for pulmonary drug delivery. Not only do they exhibit a high surface-to-volume ratio relative to spherical aerosols, but their aerodynamic properties also enable them to reach deep into the lungs. Until present, however, our understanding of the deposition characteristics of inhaled aerosols in the distal acinar lung regions has been mostly limited to spheres. To shed light on the fate of elongated aerosols in the pulmonary depths, we explore through in silico numerical simulations the deposition and dispersion characteristics of ellipsoid-shaped fibers in a physiologically-realistic acinar geometry under oscillatory breathing flow conditions mimicking various inhalation maneuvers. The transient translation and rotational movement of micron-sized elongated particles under drag, lift, and gravitational forces are simulated as a function of size (dp) and aspect ratio (AR). Our findings underscore how acinar deposition characteristics are intimately linked to the geometrical combination of dp and AR under oscillatory flow conditions. Surprisingly, the elongation of the traditionally recommended size range of spherical particles (i.e., 2-3 μm) for acinar deposition may lead to a decrease in deposition efficiency and dispersion. Instead, our findings advocate how elongating particles (i.e., high AR) in the larger size range of 4-6 μm might be leveraged for improved targeted deposition to the acinar regions. Together, these results point to new windows of opportunities in selecting the shape and size of micron-sized fibers for targeted pulmonary deposition. Such in silico efforts represent an essential stepping stone in further exploring aerosol drug carrier designs for inhalation therapy to the deep lungs.

Keywords: Acinus; CFD; Fibers; In silico; Inhalation therapy; Lungs; Targeted delivery.

MeSH terms

  • Administration, Inhalation
  • Aerosols / administration & dosage
  • Computer Simulation
  • Drug Carriers / administration & dosage*
  • Models, Biological*
  • Pulmonary Alveoli / metabolism*

Substances

  • Aerosols
  • Drug Carriers