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Pharmacokinetics and Pharmacodynamics of Drugs Delivered to the Lung
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Stefanie K. Drescher, Mong-Jen Chen, Jürgen B. Bulitta, Günther Hochhaus
Breathing lung-on-a-chip is a microfluidic three-dimensional device that reconstructs the microarchitecture and dynamic microenvironment of the alveolar-capillary unit of the living human lung. This micro-engineered lung model consists of a thin 10 µm microporous elastomeric membrane, which divides the air and blood chambers. In the upper chamber, the membrane is covered by human alveolar epithelial cells, whereas the membrane of the lower chamber is coated by pulmonary microvascular endothelial cells. To mimic the alveolar air space more realistically, the alveolar epithelial cells are exposed to air creating an air-liquid interface and breathing movements are introduced. During normal inspiration, the alveoli of the human lung will expand; this has been mimicked by a computer controlled cyclic stretching of the membrane with its adherent cell layer (Esch et al. 2015); however, this model lacks to incorporate changes in air flow and air pressure (Huh et al. 2010; Huh 2015). The lung-on-a-chip approach showed inflammatory responses to an induced alveolar bacterial infection. In addition, lung diseases such as pulmonary edema can be emulated (Huh et al. 2010; Esch et al. 2015). The suitability of this model to also probe for biopharmaceutical aspects of inhalation drug therapy still needs to be demonstrated.
Nanotechnology for Tissue Engineering and Regenerative Medicine
Published in Šeila Selimovic, Nanopatterning and Nanoscale Devices for Biological Applications, 2017
Şükran Şeker, Y. Emre Arslan, Serap Durkut, A. Eser Elçin, Y. Murat Elçin
Organ-on-a-chip systems are being used for tissue engineering and drug development studies. Huh et al. developed an actual lung-on-a-chip microfluidic device that reproduces the critical structural, functional, and mechanical properties of the human alveolar–capillary interface, which is the basic functional unit of the living lung [101]. In this study, two of the channels fabricated by soft lithography were separated by a thin (10 μm), porous, flexible membrane made of PDMS. This membrane was coated with ECM proteins (fibronectin or collagen). Then, human alveolar epithelial cells and human pulmonary microvascular endothelial cells were cultured on opposite sides of the ECM-coated membrane (Figure 14.15). The cellular response to a pulmonary infection of bacterial origin and to silica nanoparticles was demonstrated using this system. The results indicated that the developed lung-on-a-chip microfluidic device could reconstitute multiple physiological functions observed in the whole living lung. These findings have shown that this bioinspired microdevice may enhance the capabilities of cell culture models and allow low-cost alternatives to animal and clinical studies for drug screening and toxicology studies [101].
Nasal and Pulmonary Drug Delivery Systems
Published in Ambikanandan Misra, Aliasgar Shahiwala, In-Vitro and In-Vivo Tools in Drug Delivery Research for Optimum Clinical Outcomes, 2018
Pranav Ponkshe, Ruchi Amit Thakkar, Tarul Mulay, Rohit Joshi, Ankit Javia, Jitendra Amrutiya, Mahavir Chougule
One advanced in-vitro model is lung-on-a-chip, wherein the endothelial cells present on the lung lining are placed very close to blood vessels across a porous flexible boundary. Media is circulated through the blood vessels to mimic blood flow, while air is circulated on the other side. Mechanical stretching is generated by a cyclic vacuum which mimics breathing (Huh, Matthews et al. 2010). Lung-on-a-chip has been used for the screening of chemotherapeutic drug oncogene modeling, infectious disease research, and inflammatory diseases of the lung. It is a promising way of studying various lung diseases. A detailed review of its utilities is available elsewhere (Konar, Devarasetty et al. 2016).
Emerging applications of microfluidic techniques for in vitro toxicity studies of atmospheric particulate matter
Published in Aerosol Science and Technology, 2021
Fobang Liu, Nga Lee Ng, Hang Lu
The developments of microengineering approaches for 3D cell culture have been further improved to reconstitute 3D organ-level structures. Various organ-on-a-chip models have been constructed on microfluidic platforms, which recapitulate biochemical and mechanical microenvironments, in addition to having a 3D matrix for cell growth (Huh, Hamilton, and Ingber 2011). For example, in lung-on-a-chip models, air is introduced into the epithelial channel to mimic the air-liquid interface within the lung. The respiratory tract is a major route for airborne PM to enter human body. There have been a few studies using lung-on-a-chip models to evaluate the pulmonary risk of PM exposure in an organotypic manner (Huh et al. 2010; Xu et al. 2020; Zheng et al. 2019). In the model developed by Huh et al. (2010), in addition to 3D cell culture, two lateral microchambers were incorporated into the device to simulate dynamic mechanical distortion of the alveolar-capillary interface caused by breathing movements. This lung-on-a-chip model was used to study the toxicology of silica nanoparticles. Results indicate that cyclic mechanical strain contributes to the activation of pro-inflammatory activities of silica nanoparticles. Mechanical strain also enhances epithelial and endothelial uptake of nanoparticles and stimulates their transport into the underlying microvascular channel. Similarly, Xu et al. (2020) employed a lung-on-a-chip model to probe the adverse effects of ambient PM in the respiratory system (Figure 5B). The model enables investigating multiple cellular responses (e.g., ROS generation, apoptosis, and inflammatory cytokines expression) and cell-cell interactions (e.g., changes of adherens junctions and permeability of the alveolar-capillary barrier) induced by PM. Further, immunocytes could be introduced to the vessel channel forming a triple coculture system to investigate the interaction of injured tissue and immunocytes. Interestingly, an increase in permeability of the alveolar‐capillary barrier was observed in both the studies of Xu et al. (2020) and Huh et al. (2010), although different microfluidic designs and PM samples were tested in the two studies. These complexities in the tissue model could potentially push the relevance of the in vitro system toward better mimicking the physiology in vivo.