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Nanomedicines for the Treatment of Respiratory Diseases
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Brahmeshwar Mishra, Sundeep Chaurasia
Cystic fibrosis, a frequent inherited, autosomal recessive disorder. It is caused by a dysfunction of the epithelial chloride channel CFTR (cystic fibrosis transmembrane regulator) (Rosenstein and Zeitlin, 1998). So far, more than 500 mutations of the CFTR gene are known that are associated with cystic fibrosis (Stern, 1997). Apart from gastrointestinal manifestations such as pancreatic insufficiency, the major cause of morbidity results from airway disease (Rosenstein and Zeitlin, 1998). The hypersecretory-induced airway changes in cystic fibrosis are characterized by submucosal gland and goblet cell hyper- and metaplasia, leading to mucus over-production and distortion of the mucociliary clearance. As a result, airway plugging by mucus leads to chronic inflammatory changes and bacterial colonization (Groneberg et al., 2002; Ramsey, 1996).
New Approaches from Nanomedicine and Pulmonary Drug Delivery for the Treatment of Tuberculosis
Published in Ana Rute Neves, Salette Reis, Nanoparticles in Life Sciences and Biomedicine, 2018
Joana Magalhães, Alexandre C. Vieira, Soraia Pinto, Sara Pinheiro, Andreia Granja, Susana Santos, Marina Pinheiro, Salette Reis
The mucus layer is composed of inorganic salts, proteins, glycoproteins (mucins), lipids, and water; is 8 μm thick in the bronchi; and transitions through the airways into a 0.07 μm thick surfactant in the alveoli [39]. The pulmonary surfactant (PS) layer is composed of phospholipids, cholesterol, and various proteins that are released from type II epithelial cell lamellar bodies [44, 47]. Besides affecting particle dissolution and diffusion toward the epithelium, this protective coating of the lungs also affects the interactions between drugs and cell surfaces and/or receptors [39]. Apart from coughing, mucociliary clearance and macrophage clearance affect the residence time of inhaled drugs in the lungs [47]. Mucociliary clearance involves the movement of mucus under the influence of coordinated ciliary beat at the surface of airways [47, 48]. Particles can migrate through the mucus to the epithelium for absorption or, in the extreme insoluble particles, are transported by mucociliary-mediated transport [48]. Mucociliary clearance is a fast and unspecific mechanism, with 80%–90% of inhaled particles being excreted from the upper and central lung within 24 h [47]. The inhaled particles that exhibit delays in dissolution are usually taken up by macrophages and transported to lymph nodes [48]. Alveolar macrophages are able to phagocyte inhaled organic or inorganic particles. Nevertheless, in contrast to mucociliary clearance, alveolar macrophages show size-dependent uptake, being more effective for particles with a geometric diameter of 0.5–5 μm [47].
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
For the assessment of (nano)particle toxicity in the respiratory tract, advanced 3D in vitro tissue models have been emerging as promising systems over traditional two-dimensional (2D) cultures. These models contain different cell types in varied orientation and number that need to be organized in a structure that reflects the tissue of interest. These cultures are often obtained from donor-derived primary cells or from stem cells such as Induced Pluripotent Stem Cell (iPSC)), and are commonly grown in tissue-specific scaffolds (Carvalho et al. 2020; Kastlmeier et al. 2022; Langhans 2018). These models either mimic normal or diseased tissues (Jackson and Lu 2016; Sotty et al. 2019). Advanced multicellular 3D lung tissue models better reflect cellular interactions observed in vivo and, therefore, enable investigation of the cellular interplay between different cell types following (nano)particle inhalation exposure. Some of these respiratory models display active ciliary beating and mucus production that mimic mucociliary clearance defense systems (George et al. 2019; Kooter et al. 2017).