Towards More Precise Targeting of Inhaled Aerosols to Different Areas of the Respiratory System

Abstract

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during the aerosolization of liquids or powders and the role of aerosol flow dynamics in the RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Through an analysis of existing technical limitations, selected strategies aimed at enhancing the effectiveness of targeted aerosol delivery to the RS have been identified and presented. These strategies also include the use of smart inhaling devices and systems with built-in AI algorithms.

Keywords: AI in drug delivery; aerosol; airflow dynamics; inhalation; nebulization; particle deposition; particle–lung interactions; smart inhalers.

Figure 1

The basic processes and factors shaping the efficiency of drug delivery using aerosols.

Figure 2

Regional deposition (expressed as % of inhaled particles) of aerosol delivered via mouth as a function of particle size (aerodynamic diameter) for normal breathing: ET—extrathoracic deposition; TB—tracheobronchial deposition; and PUL—pulmonary deposition. Data calculated according to Multiple-Path Particle Dosimetry Model (MPPD) model for Yeh–Schum symmetric bronchial geometry [20].

Figure 3

Schematic airflow variation vs. time during inhalation and exhalation. AFR—average flow rate during inhalation; PIFR—peak inspiratory flow rate; and t_inh—time of inhalation.

Figure 4

Schematic trajectory of a few-micrometer particle moving through a bronchial bifurcation at different time instants of inhalation and the corresponding different values of the flow rate Q: (a) Q equal the peak inspiratory flow rate (PIFR), or (b) Q smaller than PIFR. Blue and red arrows represent the instantaneous forces acting on the particle due to inertia (I) and gravitation (G).

Figure 5

Visualization of aerosol penetration through reconstructed large airways of COPD patient during simulated inhalation. Bronchial geometry according to [37].

Figure 6

(a). An aerosol plume obtained with the manually actuated nasal atomizer (dashed lines schematically show the limits of the expanding plume). (b). Schematically drawn incompatibility of the expanding aerosol plume and narrow nasal airways, resulting in predominant anterior deposition of sprayed liquid (based on results published by Sosnowski et al. [65]).

Figure 7

(a). Schematic action of the composite drug–mucolytic particle in the bronchial mucus: mucus-thinning component (yellow) accelerates diffusion of the drug (blue) through the liquid layer. (b). Local reduction in the concentration of PS on the alveolar surface due to surfactant adsorption onto a porous particle. AFL—alveolar fluid layer; ∇γ—gradient of the surface tension caused by adsorption of surfactant molecules on the particle according to the concept proposed in [80].

Figure 8

Aerosol transport from VMN during inhalation and exhalation (a) without IC (FA denotes fugitive aerosol) and (b) with valved IC (only air is exhaled).