ERC

 ERC    European Commission

Unravelling respiratory microflows in silico and in vitro: novel paths for targeted pulmonary delivery in infants and young children

 

About the project

 

Fundamental research on respiratory transport phenomena, quantifying momentum and mass transfer in the lung depths, is overwhelmingly focused on adults. Yet, children are not just miniature adults; their distinct lung structures and heterogeneous ventilation patterns set them aside from their parents. In RespMicroFlows, we will break this cycle and unravel the complex microflows characterizing alveolar airflows in the developing pulmonary acini. Our discoveries will foster ground-breaking transport strategies to tackle two urgent clinical needs that burden infants and young children. The first challenge relates to radically enhancing the delivery and deposition of therapeutics using inhalation aerosols; the second involves targeting liquid bolus installations in deep airways for surfactant replacement therapy. By developing advanced in silico numerical simulations together with microfluidic in vitro platforms mimicking the pulmonary acinar environment, our efforts will not only deliver a gateway to reliably assess the outcomes of inhaling aerosols and predict deposition patterns in young populations, we will furthermore unravel the fundamentals of liquid bolus transport to achieve optimal surfactant delivery strategies in premature neonates. By recreating cellular alveolar environments that capture underlying physiological functions, our advanced acinus-on-chips will deliver both at true scale and in real time the first robust and reliable in vitro screening platforms of exogenous therapeutic materials in the context of inhaled aerosols and surfactant-laden installations. Combining advanced engineering-driven flow visualization solutions with strong foundations in transport phenomena, fluid dynamics and respiratory physiology, RespMicroFlows will pave the way to a new and unprecedented level in our understanding and quantitative mapping of respiratory flow phenomena and act as catalyst for novel targeted pulmonary drug delivery strategies in young children.

PERIOD: 2016-2021

 


The ERC team

 

Principal Investigator

Prof. Josué Sznitman

Research Associate

Dr. Arbel Artzy-Schnirman

Administrator

Mrs. Osnat Nixon

Graduate Students

Yan Ostrovski

Lihi Shachar-Berman

Eliram Nof

Former ERC team members

Dr. Prashant Das

Dr. Alessandro De-Rosis

Dr. Rami Fishler

Dr. Hagit Shtauber

Dr. Alexander Shapiro


Journal Publications

 

Bauer K, Nof E and Sznitman J. Revisiting high-frequency oscillatory ventilation in vitro and in silico in neonatal conductive airways. Clinical Biomechanics, in press.

Hofemeier P, Koshiyama K, Wada S and Sznitman J. One (sub-)acinus for all: Fate of inhaled aerosols in heterogeneous pulmonary acinar structures. European Journal of Pharmaceutical Sciences, in press.

Fishler R, Verhoeven F, de Kruijf W and Sznitman J. Particle sizing of pharmaceutical aerosols via direct imaging of particle settling velocities. European Journal of Pharmaceutical Sciences, in press.

Shachar-Berman L, Ostrovski Y, Kassinos SC and Sznitman J. Transport of ellipsoid fibers in oscillatory shear flows: implications for aerosol deposition in deep airways. European Journal of Pharmaceutical Sciences, in press.

Stauber H, Waisman D, Korin N and Sznitman J. Red blood cell (RBC) suspensions in confined microflows: Pressure-flow relationship. Medical Engineering & Physics 48: 49-54, 2017.

Fishler R, Sznitman J. Novel aerodynamic sizing method using image-based analysis of settling velocities. Inhalation 11: 21-25, 2017.

Stauber H, Waisman D, Korin N and Sznitman J. Red blood cell dynamics in microfluidic networks of pulmonary alveolar capillaries, Biomicrofluidics 11: 014103, 2017.

Fishler R, Ostrovski Y, Lu C-Y, and Sznitman J. Streamline crossing: an essential mechanism for aerosol dispersion in the pulmonary acinus, Journal of Biomechanics, 50: 222-227, 2017 .

Hofemeier P and Sznitman J. The role of anisotropic expansion for pulmonary acinar deposition. Journal of Biomechanics 49: 3543-3548, 2016.

Ostrovski Y, Hofemeier P and Sznitman J. Augmenting Regional and Targeted Delivery in the Pulmonary Acinus using Magnetic Particles, International Journal of Nanomedicine 11: 3385-3395, 2016.


Conference Proceedings

 

Fishler R, Sznitman J. Acini-on-Chip: Novel In Vitro Assessment of Particle Dynamics and Deposition in the Deep Lungs. RDD Europe 2017. Volume 1: 119-128, 2017.

Fishler R, and Sznitman J. Computer Vision-based Aerodynamic Particle Sizing: A Rapid Method for Real-time Characterization of Inhaled Aerosols. RDD Europe 2017. Volume 2: 305-308, 2017.


Invited Talks (PI)

 

Sznitman J. Systemic drug delivery via the lungs: Can we do better? International Drug Discovery Science & Technology. Osaka, Japan, July 2017.

Sznitman J. Acini-on-Chip: Novel in vitro assessments of particle dynamics and deposition in the deep lungs. Respiratory Drug Delivery Europe 2017. Nice, France, April 2017 (Podium Presentation).

Sznitman J. Paradigms of targeted aerosol delivery in the deep lungs: lessons from in vitro and in silico studies. RMIT Enabling Capability Platforms Workshop on Inhaled Therapeutics for Treating Lung & Neurodegenerative Diseases. Melbourne, Australia, November 2016.

Sznitman J. Unraveling the fate of inhaled aerosols in the pulmonary depths in silico and in vitro. Workshop on Pulmonary Drug Delivery (COST Action 1404 “SimInhale”). Prague, Czech Republic, October 2016.


Conference Presentations

 

Ostrovski Y and Sznitman J. Targeted delivery in upper airways using inhaled magnetic particles. European Aerosol Conference, Zurich, Switzerland, August 2017.

Shachar-Berman L, Ostrovski Y, De Rosis A, Koshiyama K, Wada S and Sznitman J. Exploring the fate of inhales non-spherical aerosol for systemic drug delivery. International Drug Discovery Science & Technology. Osaka, Japan, July 2017.

Ostrovski Y and Sznitman J. Point targeting in the lungs using inhaled magnetic aerosols. International Drug Discovery Science & Technology. Osaka, Japan, July 2017.

Fishler R and Sznitman J. Computer vision-based aerodynamic particle sizing: A rapid method for real-time characterization of inhaled aerosols. Respiratory Drug Delivery Europe 2017. Nice, France, April 2017 (Poster).

Bauer K and Sznitman J. Evolution from childhood to adulthood of respiratory flow behavior in bronchial airways. 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.

Ostrovski Y and Sznitman J. Targeted delivery in upper airways using inhaled magnetic particles, 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.

Shachar-Berman L, Ostrovski Y, Hofemeier P and Sznitman J. Transport and deposition of non-spherical aerosols in pulmonary acinar airways. 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.

Hofemeier P, Koshiyama K, Wada S and Sznitman J. Fate of inhaled aerosols in heterogeneous pulmonary acini, 14th International Symposium on Computer Methods in Biomechanics and Biomedical Engineering, 20-22 September 2016, Tel Aviv, Israel.

Stauber H, Waisman D, and Sznitman J. Characteristics of red blood cell perfusion in microfluidic models of pulmonary capillary networks. 5th International Conference on Micro and Nano Flows, Milano, Italy, 11-14 September 2016.

Fishler R and Sznitman J. Flow mixing and dispersion phenomena in lung-inspired microfluidics structures. 5th International Conference on Micro and Nano Flows, Milano, Italy, 11-14 September 2016.


Patents

 

Ostrovski Y and Sznitman J. Foam for pulmonary drug delivery. TECH-P-91-PC. November 2017.

Ostrovski Y and Sznitman J. Targeted delivery of aerosols of magnetized active agents. PCT/IL2017/050472. April 2017.