In silico optimization of targeted aerosol delivery in upper airways via Inhaled Volume Tracking

Heller-Algazi, Metar; Nof, Eliram; Das, Parichay K.; Bhardwaj, Saurabh; Kassinos, Stavros C.; Sznitman, Josué

doi:10.1016/j.clinbiomech.2020.105138

Cited by 6 publications

(5 citation statements)

References 45 publications

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“…1.145 l/min), the magnet assembly could merely cause a small deflection to the aerosol pulse (Fig. 6; compare SM video 2 and 3), underlining the role of aerodynamic drag forces on airborne particles during flight (Heller-Algazi et al, 2020;Ostrovski et al, 2018;. A parallel question lies in whether once the bolus is stopped above the targeted location, would it be possible to allow the particles to sediment under gravity, circumventing the need of a magnet altogether.…”

Section: Magnetic Aerosol Targeting In Bifurcating In Vitro Airwaysmentioning

confidence: 99%

“…To first model a main bronchial bifurcation, we 3d print (Form 2 printer with Clear resin, Formlabs) a carinal bifurcation that connects a 16.8 mm tracheal glass tube to two 12.65 mm bronchi-mimicking glass tubes; the model follows representative morphometric measurements in a human adult lung (Heller-Algazi et al, 2020;Ostrovski et al, 2018). The magnet is placed next to one bronchus (see Results & Discussion); experiments are filmed from above illuminated by a continuous wave laser sheet (diode pumped solid state, 532 nm wavelength, 2.26 W, LaVision GmbH).…”

Section: In Vitro Upper Airway Modelsmentioning

confidence: 99%

“…Next, we explore focused targeting in a four-generation airway model (i.e. corresponding to the first four generations of a 3D upper airway model recently introduced in in silico studies (Heller-Algazi et al, 2020;Ostrovski et al, 2018)). To quantify deposition, we 3d print the airway tree as two halves (Fig.…”

Section: In Vitro Upper Airway Modelsmentioning

confidence: 99%

“…In the current setup, in vitro experiments correspond closest to a scenario whereby a patient is intubated and mechanically ventilated. While the endotracheal intubation of the model circumvents the occurrence of aerosol dispersion phenomena due to the laryngeal jet (Das et al, 2018;Heller-Algazi et al, 2020), our first embodiment holds clinical applications in specialized inhalation therapies (Fink and Ari, 2013). With this in mind, voluntary oral inhalation through an inhaler device would significantly broaden the applicability of the technique.…”

Section: From Proof-of-concept To Clinical Applicationsmentioning

confidence: 99%

“…lung lobe) or a localized spot in the airway tree (e.g. tumors in bronchogenic carcinoma) remains generally poor (Heller-Algazi et al, 2020;Ostrovski et al, 2018;Stein and Thiel, 2017). Such drawback leads for example to higher risks of side effects and lower bioavailabilty (Velkov et al, 2014); a point particularly relevant in lung cancer (Stewart and Wild, 2014;Zarogoulidis et al, 2012a).…”

Section: Introductionmentioning

confidence: 99%

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Focused targeting of inhaled magnetic aerosols in reconstructed in vitro airway models

Ostrovski

Dorfman

Poh

et al. 2021

Journal of Biomechanics

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The pulmonary tract is an attractive route for topical treatments of lung diseases. Yet, our ability to confine the deposition of inhalation aerosols to specific lung regions, or local airways, remains still widely beyond reach. It has been hypothesized that by coupling magnetic particles to inhaled therapeutics the ability to locally target airway sites can be substantially improved. Although the underlying principle has shown promise in seminal in vivo animal experiments as well as in vitro and in silico studies, its practical implementation has come short of delivering efficient localized airway targeting. Here, we demonstrate in an in vitro proof-of-concept an inhalation framework to leverage magnetically-loaded aerosols for airway targeting in the presence of an external magnetic field. By coupling the delivery of a short pulsed bolus of sub-micron (~500 nm diameter) droplet aerosols with a custom ventilation machine that tracks the volume of air inhaled past the bolus, focused targeting can be maximized during a breath hold maneuver. Specifically, we visualize the motion of the pulsed SPION-laden (super-paramagnetic iron oxide nanoparticles) aerosol bolus and quantify under microscopy ensuing deposition patterns in reconstructed 3D airway models. Our aerosol inhalation platform allows for the first time to deposit inhaled particles to specific airway sites while minimizing undesired deposition across the remaining airspace, in an effort to significantly augment the targeting efficiency (i.e. deposition ratio between targeted and untargeted regions). Such inhalation strategy may pave the way for improved treatment outcomes, including reducing side effects in chemotherapy.

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Section: Magnetic Aerosol Targeting In Bifurcating In Vitro Airwaysmentioning

confidence: 99%

Section: In Vitro Upper Airway Modelsmentioning

confidence: 99%

Section: In Vitro Upper Airway Modelsmentioning

confidence: 99%