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 μm) 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 μm 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 μm) 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.

Ventilation-induced jet suggests biotrauma in reconstructed airways of the intubated neonate

“…Our experimental and numerical investigations revolve around the use of a morphometrically faithful model of reconstructed neonatal upper airways. This airway model (figure 5a) is based on a previously published hybrid geometry [66], following the seminal works of Weibel [67] and Horsfield et al [68]. The computer-aided design (CAD) model was homothetically scaled down to the size of an approximately 2 kg preterm neonate following previously reported methods [35].…”

Targeting inhaled aerosol delivery to upper airways in children: Insight from computational fluid dynamics (CFD)

“…mouth-throat) region follows an idealized model introduced and validated by Xi & Longest [ 53 ] and made available through RDD Online [ 57 ]. In parallel, the conductive bronchial airway tree features a morphometrically-faithful model of an average human (male) adult [ 58 ]. Briefly, the airway tree features seven generations of dichotomously branching, asymmetric airways that follows the seminal morphometric models of Weibel [ 59 ] and Horsfield [ 60 ], using previously reported methods [ 61 ].…”

Inhaled cytotoxic chemotherapy: clinical challenges, recent developments, and future prospects

“…By controlling critical patient's inspiratory parameters (e.g. inspiratory flow rate, inspiratory volume, time during the inspiration and/or moment of the breath hold manoeuver), in silico studies demonstrated the ability to adapt aerosol characteristics and delivery parameters [76,77]. 'Smart' inhalers are developed on these bases to target more specifically a zone of the respiratory tract during the inhalation procedure but they require a much higher cost that renders them difficult to use them as disposable devices.…”