Toxicity of airborne nanoparticles: Facts and challenges

Environment International, Journal Year: 2024, Volume and Issue: 190, P. 108889 - 108889

Published: July 18, 2024

Air pollution is one of the most severe environmental health hazards, and airborne nanoparticles (diameter <100 nm) are considered particularly hazardous to human health. They produced by various sources such as internal combustion engines, wood biomass burning, fuel natural gas combustion, their origin, among other parameters, determines intrinsic toxicity for reasons that not yet fully understood. Many constituents toxic or at least hazardous, including polycyclic aromatic hydrocarbons (PAHs) heavy metal compounds, in addition gaseous pollutants present aerosol fraction, NOx, SO2, ozone. All these compounds can cause oxidative stress, mitochondrial damage, inflammation lungs tissues, cellular organelles. Epidemiological investigations concluded may affect respiratory, cardiovascular, nervous systems. Moreover, particulate matter has been linked an increased risk lung cancer, a carcinogenic effect related DNA but inflammatory response pollutants, which release cytokines promotes proliferation pre-existing mutated cancer cells. The mechanisms behind be investigated experimentally using cell cultures animal models. Methods gathering have explored, standardized protocols needed ensure samples accurately represent chemical mixtures environment. Toxic studied models, designing realistic exposure settings challenging. air–liquid interface (ALI) system directly exposes cells, mimicking particle inhalation into lungs. Continuous research monitoring essential understanding effects developing active strategies mitigate risks

Language: Английский

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An integrated new approach methodology for inhalation risk assessment of safe and sustainable by design nanomaterials

Environment International, Journal Year: 2024, Volume and Issue: 183, P. 108420 - 108420

Published: Jan. 1, 2024

The production and use of nanomaterials (NMs) has increased over the last decades posing relevant questions on their risk after release exposure population or sub-populations. In this context, safe sustainable by design (SSbD) approach framework requires to assess potential hazard connected with intrinsic properties material along whole life cycle NM and/or nano enabled products. Moreover, in years, new advanced methodologies (NAMs) increasingly gained attention for alternative methods obtaining information NMs risk. Considering SSbD NAMs frameworks, within ASINA H2020 project, we developed devoted at improving definition different Ag TiO2 NPs. are considering two air liquid interface systems, Vitrocell Cloud-α Cultex Compact module steps obtain reproducible exposures described. build integration environmental monitoring campaigns nano-coating sites, allowing quantification multiple-path particle dosimetry (MPPD) model expected lung deposited dose occupational settings. Starting from information, laboratory aerosolized NPs performed using equipment human alveolar cells (epithelial macrophages), replicating doses estimated workers MPPD. Preliminary results cell viability inflammatory responses reported. proposed may represent possible future reference procedures assessing inhalation toxicology, supporting assessment real doses.

Language: Английский

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Toxicological effects of long-term continuous exposure to ambient air on human bronchial epithelial Calu-3 cells exposed at the air-liquid interface

Environmental Research, Journal Year: 2025, Volume and Issue: unknown, P. 120759 - 120759

Published: Jan. 1, 2025

Language: Английский

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The (re)emergence of aerosol delivery: Treatment of pulmonary diseases and its clinical challenges

Journal of Controlled Release, Journal Year: 2025, Volume and Issue: 379, P. 421 - 439

Published: Jan. 16, 2025

Aerosol delivery represents a rapid and non-invasive way to directly reach the lungs while escaping hepatic first-pass effect. The development of pulmonary drugs for respiratory diseases such as cystic fibrosis, lung infections, fibrosis or cancer requires an enhanced understanding relationships between natural physiology system pathophysiology these conditions. This knowledge is crucial better predict thereby control drug deposition. Moreover, aerosol administration faces several challenges, including tract, immune system, mucociliary clearance, presence fluid on airway surfaces, and, in some cases, bacterial colonisation. Each them influences bioavailability active molecule. In addition particle size device used administer treatment are critical factors that can significantly impact biodistribution drugs. Nanoparticles very promising new formulations delivery, they be fine-tuned entire tract overcome difficulties encountered along way. However, properly assess preclinical studies need more thorough efficiently enhance delivery.

Language: Английский

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Developing human upper, lower, and deep lung airway models: Combining different scaffolds and developing complex co-cultures

Journal of Tissue Engineering, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 1, 2025

Advanced in vitro models are crucial for studying human airway biology. Our objective was the development and optimization of 3D representing diverse regions, including deep lung alveolar region. This initiative aimed at assessing influence selective scaffold materials on distinct co-culture models. While PET membranes (30 µm thickness) were unsuitable due to their stiffness relatively high Young’s modulus, a combination collagenous scaffolds seeded with Calu-3 cells fibroblasts, showed increased mucus production going from week 1 4 air lift culture. Meanwhile standard electrospun polymer membrane (50–60 thick), which possesses considerably low modulus elasticity, offered higher flexibility supported co-cultures primary epithelial (huAEC) endothelial (hEC) concert biopsy-derived fibroblasts enhanced maturation tissue model. As published, designing require thin mimic required ultra-thin ECM, addition assuring right balanced AT1/AT2 ratio biomimetic representation. We concluded that co-cultivation primary/stem or cell lines has function than applied scaffolds.

Language: Английский

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Biomimetic In Vitro Lung Models: Current Challenges and Future Perspective

Advanced Materials, Journal Year: 2023, Volume and Issue: 35(13)

Published: Feb. 7, 2023

As post-COVID complications, chronic respiratory diseases are one of the foremost causes mortality. The quest for a cure this recent global challenge underlines that lack predictive in vitro lung models is main bottlenecks pulmonary preclinical drug development. Despite rigorous efforts to develop biomimetic models, current cutting-edge represent compromise numerous technological and biological aspects. Most advanced still "proof-of-concept" phase with low clinical translation findings. On other hand, advances cellular molecular studies mainly based on relatively simple unrealistic models. Herein, challenges potential strategies toward not only bioinspired but truly discussed.

Language: Английский

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Aerosol pulmonary immune engineering

Advanced Drug Delivery Reviews, Journal Year: 2023, Volume and Issue: 199, P. 114831 - 114831

Published: April 24, 2023

Aerosolization of immunotherapies poses incredible potential for manipulating the local mucosal-specific microenvironment, engaging specialized pulmonary cellular defenders, and accessing mucosal associated lymphoid tissue to redirect systemic adaptive memory responses. In this review, we breakdown key inhalable immunoengineering strategies chronic, genetic, infection-based inflammatory disorders, encompassing historic use immunomodulatory agents, transition biological inspired or derived treatments, novel approaches complexing these materials into drug delivery vehicles enhanced release outcomes. Alongside a brief description immune targets, fundamentals aerosol delivery, preclinical models response, survey recent advances inhaled immunotherapy platforms, ranging from small molecules biologics particulates cell therapies, as well prophylactic vaccines. each section, address formulation design constraints advantages platform in driving desirable modifications. Finally, prospects clinical translation outlook engineering are discussed.

Language: Английский

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Advanced 3D In Vitro Lung Fibrosis Models: Contemporary Status, Clinical Uptake, and Prospective Outlooks

ACS Biomaterials Science & Engineering, Journal Year: 2024, Volume and Issue: 10(3), P. 1235 - 1261

Published: Feb. 9, 2024

Fibrosis has been characterized as a global health problem and ranks one of the primary causes organ dysfunction. Currently, there is no cure for pulmonary fibrosis, limited therapeutic options are available due to an inadequate understanding disease pathogenesis. The absence advanced in vitro models replicating dynamic temporal changes observed tissue with progression significant impediment development novel antifibrotic treatments, which motivated research on tissue-mimetic three-dimensional (3D) models. In this review, we summarize emerging trends preparing lung recapitulate biochemical biomechanical processes associated fibrogenesis. We begin by describing importance vivo studies highlighting often poor correlation between preclinical clinical outcomes limitations conventional cell culture accurately simulating 3D microenvironment. Rapid advancement biomaterials, biofabrication, biomicrofluidics, related bioengineering techniques enabling preparation reproduce epithelium structure operate reliable drug screening strategies precise prediction. Improving these model systems necessary find cross-talks growing cells stage at myofibroblasts differentiate. These allow us utilize knowledge identify, characterize, hand pick medicines beneficial human community. challenges current approaches, along opportunities further potential translation field, presented toward developing treatments fibrosis.

Language: Английский

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Recent Developments in Aerosol Pulmonary Drug Delivery: New Technologies, New Cargos, and New Targets

Annual Review of Biomedical Engineering, Journal Year: 2024, Volume and Issue: 26(1), P. 307 - 330

Published: March 1, 2024

There is nothing like a global pandemic to motivate the need for improved respiratory treatments and mucosal vaccines. Stimulated by COVID-19 pandemic, pulmonary aerosol drug delivery has seen flourish of activity, building on prior decades innovation in particle engineering, inhaler device technologies, clinical understanding. As such, field expanded into new directions working toward efficient increasingly complex cargos address wider range diseases. This review seeks highlight recent innovations approaches personalize inhalation delivery, deliver cargos, diversify targets treated prevented through delivery. We aim inform readers emerging efforts within predict where future breakthroughs are expected impact treatment

Language: Английский

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Aerosol exposure at air-liquid-interface (AE-ALI) in vitro toxicity system characterisation: Particle deposition and the importance of air control responses

Toxicology in Vitro, Journal Year: 2024, Volume and Issue: 100, P. 105889 - 105889

Published: July 5, 2024

Language: Английский

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