Deposition Mechanisms

Abstract

The success of inhalation therapy is not only dependent upon the pharmacology of the drugs being inhaled but also upon the site and extent of deposition in the respiratory tract. Similarly, the toxicity of environmental and industrial particulate matter is affected not only by the nature of the dust but also by the amount and spatial distribution of deposited particles in the lung. Aerosol deposition is primarily governed by the mechanisms of inertial impaction, gravitational sedimentation, Brownian diffusion, and, to a lesser extent, by turbulence, electrostatic precipitation, and interception. The relative contribution of these different mechanisms is a function of the physical characteristics of the particles, the lung structure, and the flow patterns. Large particles (>5 lm) tend to deposit mainly in the upper and large airways, limiting the amount of aerosols that can be delivered to the lung. Small particles (<2 lm) deposit mainly in the alveolar region, whereas particles in the size range 2-5 lm deposit preferentially in the central and small airways.

A quantitative analysis of extension and distribution of lung injury in COVID-19: a prospective study based on chest computed tomography

“…A complementary explanation is provided by the physics of the deposition of inhaled viral particles. Particles of the size of the virion (0.15 μm), deposit mainly in the terminal alveolar region [ 30 ], being scarcely affected by inertial impaction or gravitational sedimentation on airways walls. The following phase is characterized by an inflammatory pattern that spreads centripetally, possibly following the direction imposed by the ciliar beats on mucus and the watery periciliary liquid [ 31 ].…”

Targeting of Inhaled Therapeutics to the Small Airways: Nanoleucine Carrier Formulations

“…Regional deposition within the LRT may also be critical for effective drug delivery [1]. Traditionally, the LRT has been divided into two principal regions: (1) the conducting airways comprising the large airways, bronchioles and terminal bronchioles which extend from generation 0 to generation 15, and (2) the respiratory zone comprising the respiratory bronchioles in generations 16-19 and the alveolar ducts and alveoli in generations 20-23.…”

“…For particles to be deposited in the lung periphery, they must first bypass inertial impaction in the URT and large airways, after which they must sediment in the small airways or alveoli before being exhaled [1]. The Stokes number (Stk) defines the tendency that a particle will diverge from the airflow and deposit by inertial impaction in the respiratory tract, Equation (1):…”

Experimental Evaluation of Dry Powder Inhalers During In- and Exhalation Using a Model of the Human Respiratory System (xPULM™)

“…Darquenne defines the primary mechanisms as the following: inertial impaction, gravitational sedimentation, Brownian diffusion, turbulent deposition, electrostatic precipitation, and interception. 23 Tsuda et al state 24 that how aerosol particles are affected by deposition mechanisms depends on the particle characteristics such as particle size, overall size distribution, shape, composition, surface characteristics and charge. Moreover, the processes resulting from molecular transfer between particles and their respective surrounding gas are nucleation, condensation, evaporation and hygroscopicity.…”

“…The described mechanisms arise mostly in the upper and conducting airway region of the respiratory tract, whereas diffusion and electrostatic precipitation is also taking place in the acinus region of the pulmonary system for particles <3 µm. 23 The objective of this work is to experimentally investigate changes in aerosol particle diameter and particle number concentration of pharmaceutical aerosols under realistic inhalation and exhalation conditions, resulting in a calculated total lung deposition. The active respiratory system model (xPULM) used in this work includes two core elements; a CT-derived upper airway model, and a primed porcine lung serving as human lung equivalent.…”