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Inhalation Drug Products Containing Nanomaterials
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Sandro R.P. da Rocha, Rodrigo S. Heyder, Elizabeth R. Bielski, Ailin Guo, Martina Steinmaurer, Joshua J. Reineke
In the respiratory airways of the lungs, alveolar macrophages are the major contributor to nanoparticle clearance. Particles deposited in the alveolar region that are engulfed by alveolar macrophages will either be degraded by enzymes in lysosomes or transported to lymph nodes via lymphatics. A small proportion of particle-carrying alveolar macrophages will migrate from alveolar regions to the start of the ciliated airways where they are cleared by mucociliary clearance. Activation of alveolar macrophages may cause the release of immunological mediators (e.g. IL-1b, IL-8, TNF-a) that can cause subsequent pulmonary inflammation (Manke et al. 2013). The choice of nanoparticles in IDPCNs should be selected to minimize such inflammatory interactions. Macrophage uptake may be limited for nanoparticles <100 nm as epithelial uptake is more efficient (Zhang et al. 2011) for this size range. Additionally, surface modification approaches (such as PEGylation) may reduce/delay macrophage uptake (Kolte et al. 2017).
Nanotoxicity and Possible Health Risks
Published in Costas Demetzos, Stergios Pispas, Natassa Pippa, Drug Delivery Nanosystems, 2019
Elena Vlastou, Efstathios P. Efstathopoulos, Maria Gazouli
Biological clearance is the physical mechanism in charge of NP expulsion from the human body. The physicochemical characteristics, entry route, and region of accumulation of NPs define the series of procedures that occur after NPs interact with humans. NPs caught by the mucosa lining in the nasopharyngeal and tracheobronchial regions could be expelled through the mouth or be transported to the GI system. Particles located in the alveolar region are possibly trapped and destroyed by the alveolar macrophages through phagocytosis. This procedure constitutes clearance of one-third of the inhaled NPs and depends upon the macrophages’ capability to recognize and attack the specific intruders [9, 25]. In case alveolar phagocytosis does not take place, soluble NPs are engulfed and expelled through the digestive system while nondegradable NPs may get transported to epithelial sites and pass into the circulatory system.
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
During breathing, there is continuous exposure to materials of myriad sizes and sources, such as bacteria (0.2–200 μm), tobacco smoke (0.01–1 μm), and pollen (20–90 μm). These particles tend to deposit along the respiratory tract from conducting airways down to the lower region of the respiratory tract. Particles are cleared rapidly by cilia in the upper airway, within the mucous layer that lines to the throat via the epithelia in the upper airways, while getting swallowed and metabolized. A barrier to absorption is posed by the pulmonary epithelium which is thick (50–60 μm) in the trachea. The epithelium diminishes to a thickness of 0.2 μm in the alveoli as we move towards the lower airways. In the lower airways, a gas exchange occurs. There is a vast surface area of alveoli approximately 43–102 m2 (in an adult) which provides access to the entire systemic circulation along with highly vascularized expanse (Gehr, Bachofen et al. 1978). Alveolar macrophages also are known as cells of the immune system that protect alveoli by scavenging foreign materials along the surface of lungs. However, there is a possibility of particles that are too small or too large to escape phagocytosis. Dendritic cells are also present throughout the airways where they evaluate pathogens and foreign substances.
Extracellular vesicles released in response to respiratory exposures: implications for chronic disease
Published in Journal of Toxicology and Environmental Health, Part B, 2018
Birke J. Benedikter, Emiel F. M. Wouters, Paul H. M. Savelkoul, Gernot G. U. Rohde, Frank R. M. Stassen
In healthy lungs, alveolar macrophages and pulmonary epithelium act in concert to rapidly clear inhaled substances and maintain an anti-inflammatory state. EV from alveolar macrophages contribute to this anti-inflammatory state by delivering suppressor of cytokine signaling (SOCS) 1 and 3 to epithelial cells (Bourdonnay et al. 2015). Importantly, CS-exposed mice and human smokers exhibited decreased SOCS concentrations in BALF compared to nonsmoking controls, suggesting a loss of EV-dependent anti-inflammatory state in smokers (Bourdonnay et al. 2015). In addition, the anti-inflammatory effect of alveolar macrophage-derived EV depends upon their internalization by target cells, which is inhibited by the presence of CS extract (CSE) (Schneider et al. 2017).
Assessing the in vitro toxicity of airborne (nano)particles to the human respiratory system: from basic to advanced models
Published in Journal of Toxicology and Environmental Health, Part B, 2023
Maria João Bessa, Fátima Brandão, Fernanda Rosário, Luciana Moreira, Ana Teresa Reis, Vanessa Valdiglesias, Blanca Laffon, Sónia Fraga, João Paulo Teixeira
Coculture models have been developed to resemble the complexity of the human airways by combining airway epithelial cells together with fibroblasts, endothelial cells, airway smooth muscle cells, as well as immune cells including macrophages, dendritic, and mast cells. These models contribute to a better understanding of the toxicology and translocation mechanisms of (nano)particles (Bierkandt et al. 2018; Braakhuis et al. 2015). Table 3 summarizes some studies that assessed the effects of (nano)particle exposure in human cocultures of different regions of the lung barrier. One of the most studied regions is the bronchial epithelium since it plays a critical role in biological stress responses to inhaled (nano)particles (Jia, Wang, and Liu 2017). It is noteworthy that nano-sized particle deposition occurs in the respiratory tract primarily in the alveolar region (Londahl et al. 2014). Therefore, alveolar epithelial cells are relevant models for the toxicity of inhalable (nano)particles, particularly in the assessment of particle retention and translocation through these cells (Leibrock et al. 2019). For this purpose, in vitro models representative of the alveolar-capillary and/or air-blood barrier are also explored in (nano)toxicity assessments. The air-blood barrier is predominantly composed of alveolar epithelial cells and macrophages, that function as a structural and immunological barrier to environmental aggressors, such as fine and nano-sized particles (Kletting et al. 2018). For the alveolar region, A549 is the most frequently used cell line for assessment of (nano)particle toxicity. These cells are often used either as monocultures or in cocultures with other cell lines such as immune cells or macrophages (Fröhlich 2018). Alveolar macrophages, in turn, are important regulators of the inflammatory processes in the lung and ingest nano-sized particles as a clearance defense mechanism (Geiser 2010). THP-1 cells are a commonly used cell line for investigating in vitro function and regulation of monocytes and macrophages.