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Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

ABSTRACT: The pulmonary route presents an attractive delivery pathway for topical treatment of lung diseases. While significant progress has been achieved in understanding the physical underpinnings of aerosol deposition in the lungs, our ability to target or confine the deposition of inhalation aerosols to specific lung regions remains meagre. Here, we present a novel inhalation proof-of-concept in silico for regional targeting in the upper airways, quantitatively supported by computational fluid dynamics (CFD) simulations of inhaled micron-sized particles (i.e. 1-10 ?m) using an intubated, anatomically-realistic, multi-generation airway tree model. Our targeting strategy relies on selecting the particle release time, whereby a short-pulsed bolus of aerosols is injected into the airways and the inhaled volume of clean air behind the bolus is tracked to reach a desired inhalation depth (i.e. airway generations). A breath hold maneuver then follows to facilitate deposition, via sedimentation, before exhalation resumes and remaining airborne particles are expelled. Our numerical findings showcase how particles in the range 5-10 ?m combined with such inhalation methodology are best suited to deposit in the upper airways, with deposition fractions between 0.68 and unity. In contrast, smaller (< 2 ?m) particles are less than optimal due to their slow sedimentation rates. We illustrate further how modulating the volume inhaled behind the pulsed bolus, prior to breath hold, may be leveraged to vary the targeted airway sites. We discuss the feasibility of the proposed inhalation framework and how it may help pave the way for specialized topical lung treatments.

SUBMITTER: Ostrovski Y

PROVIDER: S-EPMC6445363 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

Ostrovski Yan Y Dorfman Simon S Mezhericher Maksim M Kassinos Stavros S Sznitman Josué J

Flow, turbulence and combustion 20180502 1

The pulmonary route presents an attractive delivery pathway for topical treatment of lung diseases. While significant progress has been achieved in understanding the physical underpinnings of aerosol deposition in the lungs, our ability to target or confine the deposition of inhalation aerosols to specific lung regions remains meagre. Here, we present a novel inhalation proof-of-concept <i>in silico</i> for regional targeting in the upper airways, quantitatively supported by computational fluid ...[more]

PMID: 30956537

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Project description:The inhalation route has a substantial influence on the fate of inhaled particles. An outbreak of infectious diseases such as COVID-19, influenza or tuberculosis depends on the site of deposition of the inhaled pathogens. But the knowledge of respiratory deposition is important also for occupational safety or targeted delivery of inhaled pharmaceuticals. Simulations utilizing computational fluid dynamics are becoming available to a wide spectrum of users and they can undoubtedly bring detailed predictions of regional deposition of particles. However, if those simulations are to be trusted, they must be validated by experimental data. This article presents simulations and experiments performed on a geometry of airways which is available to other users and thus those results can be used for intercomparison between different research groups. In particular, three hypotheses were tested. First: Oral breathing and combined breathing are equivalent in terms of particle deposition in TB airways, as the pressure resistance of the nasal cavity is so high that the inhaled aerosol flows mostly through the oral cavity in both cases. Second: The influence of the inhalation route (nasal, oral or combined) on the regional distribution of the deposited particles downstream of the trachea is negligible. Third: Simulations can accurately and credibly predict deposition hotspots. The maximum spatial resolution of predicted deposition achievable by current methods was searched for. The simulations were performed using large-eddy simulation, the flow measurements were done by laser Doppler anemometry and the deposition has been measured by positron emission tomography in a realistic replica of human airways. Limitations and sources of uncertainties of the experimental methods were identified. The results confirmed that the high-pressure resistance of the nasal cavity leads to practically identical velocity profiles, even above the glottis for the mouth, and combined mouth and nose breathing. The distribution of deposited particles downstream of the trachea was not influenced by the inhalation route. The carina of the first bifurcation was not among the main deposition hotspots regardless of the inhalation route or flow rate. On the other hand, the deposition hotspots were identified by both CFD and experiments in the second bifurcation in both lungs, and to a lesser extent also in both the third bifurcations in the left lung.

Dataset Information

Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

Publications

Targeted Drug Delivery to Upper Airways Using a Pulsed Aerosol Bolus and Inhaled Volume Tracking Method.

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