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Nanotoxicology and Lung Diseases

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Toxicology".

Deadline for manuscript submissions: closed (15 October 2014) | Viewed by 141531

Special Issue Editor


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Guest Editor
Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, USA
Interests: cellular and molecular mechanisms through which toxic environmental agents cause lung diseases; especially pulmonary fibrosis and asthma; lung fibrosis; asthma; nanotoxicology; metals; particles; fibers

Special Issue Information

Dear Colleagues,

The nanotechnology industry is rapidly developing, resulting in the production of a variety of engineered nanomaterials (ENMs) for a variety of applications. These ENMs include carbon nanotubes and metal or metal oxide nanoparticles such as zinc, titanium, cerium and silver that are incorporated into consumer products or encountered in occupational settings. Some of these novel engineered nanostructures represent a potential human health risk, due to the possibility of inhalation exposure and evidence that the lung, as well as other systemic sites, are targets for hazardous effects. Articles in this special issue will address cutting edge research aimed at elucidating the mechanisms through which ENMs cause pulmonary disease in rodents after lung exposure. Inhalation studies in rodents show that ENMs deposit within the distal regions in the lungs and cause inflammation, fibrosis, or alter immune responses. Because novel engineering methodology is resulting in the production of an increasing complexity of ENM structures that vary in toxicological activity, this issue will also address high content screening for the development of structure-activity relationships relevant to inhalation toxicity and safer design of nanoparticles. This will include exploration of factors that mediate toxic effects such as high aspect ratio, durability, and residual metal content. Finally, we will address how susceptibility factors, both genetic and environmental, determine pulmonary and systemic toxicity to ENMs.

Prof. Dr. James C. Bonner
Guest Editor

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Keywords

  • nanoparticles
  • lung
  • toxicity
  • asthma
  • fibrosis
  • immunity

Published Papers (13 papers)

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Research

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963 KiB  
Article
Comprehensive DNA Adduct Analysis Reveals Pulmonary Inflammatory Response Contributes to Genotoxic Action of Magnetite Nanoparticles
by Kousuke Ishino, Tatsuya Kato, Mamoru Kato, Tatsuhiro Shibata, Masatoshi Watanabe, Keiji Wakabayashi, Hitoshi Nakagama and Yukari Totsuka
Int. J. Mol. Sci. 2015, 16(2), 3474-3492; https://doi.org/10.3390/ijms16023474 - 4 Feb 2015
Cited by 37 | Viewed by 6326
Abstract
Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind [...] Read more.
Nanosized-magnetite (MGT) is widely utilized in medicinal and industrial fields; however, its toxicological properties are not well documented. In our previous report, MGT showed genotoxicity in both in vitro and in vivo assay systems, and it was suggested that inflammatory responses exist behind the genotoxicity. To further clarify mechanisms underlying the genotoxicity, a comprehensive DNA adduct (DNA adductome) analysis was conducted using DNA samples derived from the lungs of mice exposed to MGT. In total, 30 and 42 types of DNA adducts were detected in the vehicle control and MGT-treated groups, respectively. Principal component analysis (PCA) against a subset of DNA adducts was applied and several adducts, which are deduced to be formed by inflammation or oxidative stress, as the case of etheno-deoxycytidine (εdC), revealed higher contributions to MGT exposure. By quantitative-LC-MS/MS analysis, εdC levels were significantly higher in MGT-treated mice than those of the vehicle control. Taken together with our previous data, it is suggested that inflammatory responses might be involved in the genotoxicity induced by MGT in the lungs of mice. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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1315 KiB  
Article
Effect of Fiber Length on Carbon Nanotube-Induced Fibrogenesis
by Amruta Manke, Sudjit Luanpitpong, Chenbo Dong, Liying Wang, Xiaoqing He, Lori Battelli, Raymond Derk, Todd A. Stueckle, Dale W. Porter, Tina Sager, Honglei Gou, Cerasela Zoica Dinu, Nianqiang Wu, Robert R. Mercer and Yon Rojanasakul
Int. J. Mol. Sci. 2014, 15(5), 7444-7461; https://doi.org/10.3390/ijms15057444 - 29 Apr 2014
Cited by 68 | Viewed by 8830
Abstract
Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding [...] Read more.
Given their extremely small size and light weight, carbon nanotubes (CNTs) can be readily inhaled by human lungs resulting in increased rates of pulmonary disorders, particularly fibrosis. Although the fibrogenic potential of CNTs is well established, there is a lack of consensus regarding the contribution of physicochemical attributes of CNTs on the underlying fibrotic outcome. We designed an experimentally validated in vitro fibroblast culture model aimed at investigating the effect of fiber length on single-walled CNT (SWCNT)-induced pulmonary fibrosis. The fibrogenic response to short and long SWCNTs was assessed via oxidative stress generation, collagen expression and transforming growth factor-beta (TGF-β) production as potential fibrosis biomarkers. Long SWCNTs were significantly more potent than short SWCNTs in terms of reactive oxygen species (ROS) response, collagen production and TGF-β release. Furthermore, our finding on the length-dependent in vitro fibrogenic response was validated by the in vivo lung fibrosis outcome, thus supporting the predictive value of the in vitro model. Our results also demonstrated the key role of ROS in SWCNT-induced collagen expression and TGF-β activation, indicating the potential mechanisms of length-dependent SWCNT-induced fibrosis. Together, our study provides new evidence for the role of fiber length in SWCNT-induced lung fibrosis and offers a rapid cell-based assay for fibrogenicity testing of nanomaterials with the ability to predict pulmonary fibrogenic response in vivo. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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2346 KiB  
Article
The Effect of Size on Ag Nanosphere Toxicity in Macrophage Cell Models and Lung Epithelial Cell Lines Is Dependent on Particle Dissolution
by Raymond F. Hamilton, Sarah Buckingham and Andrij Holian
Int. J. Mol. Sci. 2014, 15(4), 6815-6830; https://doi.org/10.3390/ijms15046815 - 22 Apr 2014
Cited by 71 | Viewed by 9558
Abstract
Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage [...] Read more.
Silver (Ag) nanomaterials are increasingly used in a variety of commercial applications. This study examined the effect of size (20 and 110 nm) and surface stabilization (citrate and PVP coatings) on toxicity, particle uptake and NLRP3 inflammasome activation in a variety of macrophage and epithelial cell lines. The results indicated that smaller Ag (20 nm), regardless of coating, were more toxic in both cell types and most active in the THP-1 macrophages. TEM imaging demonstrated that 20 nm Ag nanospheres dissolved more rapidly than 110 nm Ag nanospheres in acidic phagolysosomes consistent with Ag ion mediated toxicity. In addition, there were some significant differences in epithelial cell line in vitro exposure models. The order of the epithelial cell lines’ sensitivity to Ag was LA4 > MLE12 > C10. The macrophage sensitivity to Ag toxicity was C57BL/6 AM > MARCO null AM, which indicated that the MARCO receptor was involved in uptake of the negatively charged Ag particles. These results support the idea that Ag nanosphere toxicity and NLRP3 inflammasome activation are determined by the rate of surface dissolution, which is based on relative surface area. This study highlights the importance of utilizing multiple models for in vitro studies to evaluate nanomaterials. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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2072 KiB  
Article
Comparative Pulmonary Toxicity of Two Ceria Nanoparticles with the Same Primary Size
by Lu Peng, Xiao He, Peng Zhang, Jing Zhang, Yuanyuan Li, Junzhe Zhang, Yuhui Ma, Yayun Ding, Zhenqiang Wu, Zhifang Chai and Zhiyong Zhang
Int. J. Mol. Sci. 2014, 15(4), 6072-6085; https://doi.org/10.3390/ijms15046072 - 10 Apr 2014
Cited by 40 | Viewed by 7633
Abstract
Ceria nanoparticles (nano-ceria) have recently gained a wide range of applications, which might pose unwanted risks to both the environment and human health. The greatest potential for the environmental discharge of nano-ceria appears to be in their use as a diesel fuel additive. [...] Read more.
Ceria nanoparticles (nano-ceria) have recently gained a wide range of applications, which might pose unwanted risks to both the environment and human health. The greatest potential for the environmental discharge of nano-ceria appears to be in their use as a diesel fuel additive. The present study was designed to explore the pulmonary toxicity of nano-ceria in mice after a single exposure via intratracheal instillation. Two types of nano-ceria with the same distribution of a primary size (3–5 nm), but different redox activity, were used: Ceria-p, synthesized by a precipitation route, and Ceria-h, synthesized by a hydrothermal route. Both Ceria-p and Ceria-h induced oxidative stress, inflammatory responses and cytotoxicity in mice, but their toxicological profiles were quite different. The mean size of Ceria-p agglomerates was much smaller compared to Ceria-h, thereby causing a more potent acute inflammation, due to their higher number concentration of agglomerates and higher deposition rate in the deep lung. Ceria-h had a higher reactivity to catalyzing the generation of reactive oxygen species (ROS), and caused two waves of lung injury: bronchoalveolar lavage (BAL) inflammation and cytotoxicity in the early stage and redox-activity-evoked lipid peroxidation and pro-inflammation in the latter stage. Therefore, the size distribution of ceria-containing agglomerates in the exhaust, as well as their surface chemistry are essential characteristics to assess the potential risks of using nano-ceria as a fuel additive. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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320 KiB  
Article
Effect of Nanoparticles Exposure on Fractional Exhaled Nitric Oxide (FENO) in Workers Exposed to Nanomaterials
by Wei-Te Wu, Hui-Yi Liao, Yu-Teh Chung, Wan-Fen Li, Tsui-Chun Tsou, Lih-Ann Li, Ming-Hsiu Lin, Jiune-Jye Ho, Trong-Neng Wu and Saou-Hsing Liou
Int. J. Mol. Sci. 2014, 15(1), 878-894; https://doi.org/10.3390/ijms15010878 - 9 Jan 2014
Cited by 47 | Viewed by 8145
Abstract
Fractional exhaled nitric oxide (FENO) measurement is a useful diagnostic test of airway inflammation. However, there have been few studies of FENO in workers exposed to nanomaterials. The purpose of this study was to examine the effect of nanoparticle (NP) exposure on FENO [...] Read more.
Fractional exhaled nitric oxide (FENO) measurement is a useful diagnostic test of airway inflammation. However, there have been few studies of FENO in workers exposed to nanomaterials. The purpose of this study was to examine the effect of nanoparticle (NP) exposure on FENO and to assess whether the FENO is increased in workers exposed to nanomaterials (NM). In this study, both exposed workers and non-exposed controls were recruited from NM handling plants in Taiwan. A total of 437 subjects (exposed group = 241, non-exposed group = 196) completed the FENO and spirometric measurements from 2009–2011. The authors used a control-banding (CB) matrix to categorize the risk level of each participant. In a multivariate linear regression analysis, this study found a significant association between risk level 2 of NP exposure and FENO. Furthermore, asthma, allergic rhinitis, peak expiratory flow rate (PEFR), and NF-κB were also significantly associated with FENO. When the multivariate logistic regression model was adjusted for confounders, nano-TiO2 in all of the NM exposed categories had a significantly increased risk in FENO > 35 ppb. This study found associations between the risk level of NP exposure and FENO (particularly noteworthy for Nano-TiO2). Monitoring FENO in the lung could open up a window into the role nitric oxide (NO) may play in pathogenesis. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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324 KiB  
Article
Carbon Nanotube-Induced Pulmonary Granulomatous Disease: Twist1 and Alveolar Macrophage M1 Activation
by Barbara P. Barna, Isham Huizar, Anagha Malur, Matthew McPeek, Irene Marshall, Mark Jacob, Larry Dobbs, Mani S. Kavuru and Mary Jane Thomassen
Int. J. Mol. Sci. 2013, 14(12), 23858-23871; https://doi.org/10.3390/ijms141223858 - 6 Dec 2013
Cited by 24 | Viewed by 6669
Abstract
Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated [...] Read more.
Sarcoidosis, a chronic granulomatous disease of unknown cause, has been linked to several environmental risk factors, among which are some that may favor carbon nanotube formation. Using gene array data, we initially observed that bronchoalveolar lavage (BAL) cells from sarcoidosis patients displayed elevated mRNA of the transcription factor, Twist1, among many M1-associated genes compared to healthy controls. Based on this observation we hypothesized that Twist1 mRNA and protein expression might become elevated in alveolar macrophages from animals bearing granulomas induced by carbon nanotube instillation. To address this hypothesis, wild-type and macrophage-specific peroxisome proliferator-activated receptor gamma (PPARγ) knock out mice were given oropharyngeal instillation of multiwall carbon nanotubes (MWCNT). BAL cells obtained 60 days later exhibited significantly elevated Twist1 mRNA expression in granuloma-bearing wild-type or PPARγ knock out alveolar macrophages compared to sham controls. Overall, Twist1 expression levels in PPARγ knock out mice were higher than those of wild-type. Concurrently, BAL cells obtained from sarcoidosis patients and healthy controls validated gene array data: qPCR and protein analysis showed significantly elevated Twist1 in sarcoidosis compared to healthy controls. In vitro studies of alveolar macrophages from healthy controls indicated that Twist1 was inducible by classical (M1) macrophage activation stimuli (LPS, TNFα) but not by IL-4, an inducer of alternative (M2) macrophage activation. Findings suggest that Twist1 represents a PPARγ-sensitive alveolar macrophage M1 biomarker which is induced by inflammatory granulomatous disease in the MWCNT model and in human sarcoidosis. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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Review

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877 KiB  
Review
The Role of Autophagy as a Mechanism of Toxicity Induced by Multi-Walled Carbon Nanotubes in Human Lung Cells
by Tamotsu Tsukahara, Yoshikaszu Matsuda and Hisao Haniu
Int. J. Mol. Sci. 2015, 16(1), 40-48; https://doi.org/10.3390/ijms16010040 - 23 Dec 2014
Cited by 26 | Viewed by 7173
Abstract
Carbon nanotubes (CNTs) are promising nanomaterials having unique physical and chemical properties, with applications in a variety of fields. In this review, we briefly summarize the intrinsic properties of highly purified multi-walled CNTs (MWCNTs, HTT2800) and their potential hazardous effects on intracellular and [...] Read more.
Carbon nanotubes (CNTs) are promising nanomaterials having unique physical and chemical properties, with applications in a variety of fields. In this review, we briefly summarize the intrinsic properties of highly purified multi-walled CNTs (MWCNTs, HTT2800) and their potential hazardous effects on intracellular and extracellular pathways, which alter cellular signaling and impact major cell functions such as differentiation, reactive oxygen species (ROS) production, apoptosis, and autophagy. A recent study suggested that the induction of autophagy by CNTs causes nanotoxicity. Autophagy was recently recognized as a critical cell death pathway, and autophagosome accumulation has been found to be associated with exposure to CNTs. Although autophagy is considered as a cytoprotective process, it is often observed in association with cell death, and the relationship between autophagy and cell death remains unclear. Our recent study suggests that the levels of autophagy-related genes (LC3B) and autophagosome formation are clearly up-regulated, along with an increase in numbers of autophagosome vacuoles. This review highlights the importance of autophagy as an emerging mechanism of CNT toxicity. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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4802 KiB  
Review
Inhalation of Silver Nanomaterials—Seeing the Risks
by Ioannis G. Theodorou, Mary P. Ryan, Teresa D. Tetley and Alexandra E. Porter
Int. J. Mol. Sci. 2014, 15(12), 23936-23974; https://doi.org/10.3390/ijms151223936 - 22 Dec 2014
Cited by 43 | Viewed by 11931
Abstract
Demand for silver engineered nanomaterials (ENMs) is increasing rapidly in optoelectronic and in health and medical applications due to their antibacterial, thermal, electrical conductive, and other properties. The continued commercial up-scaling of ENM production and application needs to be accompanied by an understanding [...] Read more.
Demand for silver engineered nanomaterials (ENMs) is increasing rapidly in optoelectronic and in health and medical applications due to their antibacterial, thermal, electrical conductive, and other properties. The continued commercial up-scaling of ENM production and application needs to be accompanied by an understanding of the occupational health, public safety and environmental implications of these materials. There have been numerous in vitro studies and some in vivo studies of ENM toxicity but their results are frequently inconclusive. Some of the variability between studies has arisen due to a lack of consistency between experimental models, since small differences between test materials can markedly alter their behaviour. In addition, the propensity for the physicochemistry of silver ENMs to alter, sometimes quite radically, depending on the environment they encounter, can profoundly alter their bioreactivity. Consequently, it is important to accurately characterise the materials before use, at the point of exposure and at the nanomaterial-tissue, or “nanobio”, interface, to be able to appreciate their environmental impact. This paper reviews current literature on the pulmonary effects of silver nanomaterials. We focus our review on describing whether, and by which mechanisms, the chemistry and structure of these materials can be linked to their bioreactivity in the respiratory system. In particular, the mechanisms by which the physicochemical properties (e.g., aggregation state, morphology and chemistry) of silver nanomaterials change in various biological milieu (i.e., relevant proteins, lipids and other molecules, and biofluids, such as lung surfactant) and affect subsequent interactions with and within cells will be discussed, in the context not only of what is measured but also of what can be visualized. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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728 KiB  
Review
Lung Injury Induced by TiO2 Nanoparticles Depends on Their Structural Features: Size, Shape, Crystal Phases, and Surface Coating
by Jiangxue Wang and Yubo Fan
Int. J. Mol. Sci. 2014, 15(12), 22258-22278; https://doi.org/10.3390/ijms151222258 - 3 Dec 2014
Cited by 103 | Viewed by 7805
Abstract
With the rapid development of nanotechnology, a variety of engineered nanoparticles (NPs) are being produced. Nanotoxicology has become a hot topic in many fields, as researchers attempt to elucidate the potential adverse health effects of NPs. The biological activity of NPs strongly depends [...] Read more.
With the rapid development of nanotechnology, a variety of engineered nanoparticles (NPs) are being produced. Nanotoxicology has become a hot topic in many fields, as researchers attempt to elucidate the potential adverse health effects of NPs. The biological activity of NPs strongly depends on physicochemical parameters but these are not routinely considered in toxicity screening, such as dose metrics. In this work, nanoscale titanium dioxide (TiO2), one of the most commonly produced and widely used NPs, is put forth as a representative. The correlation between the lung toxicity and pulmonary cell impairment related to TiO2 NPs and its unusual structural features, including size, shape, crystal phases, and surface coating, is reviewed in detail. The reactive oxygen species (ROS) production in pulmonary inflammation in response to the properties of TiO2 NPs is also briefly described. To fully understand the potential biological effects of NPs in toxicity screening, we highly recommend that the size, crystal phase, dispersion and agglomeration status, surface coating, and chemical composition should be most appropriately characterized. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
3462 KiB  
Review
Right or Left: The Role of Nanoparticles in Pulmonary Diseases
by Xuefei Lu, Tao Zhu, Chunying Chen and Ying Liu
Int. J. Mol. Sci. 2014, 15(10), 17577-17600; https://doi.org/10.3390/ijms151017577 - 29 Sep 2014
Cited by 73 | Viewed by 11063
Abstract
Due to the rapid development of the nanotechnology industry in the last decade, nanoparticles (NPs) are omnipresent in our everyday life today. Many nanomaterials have been engineered for medical purposes. These purposes include therapy for pulmonary diseases. On other hand, people are endeavoring [...] Read more.
Due to the rapid development of the nanotechnology industry in the last decade, nanoparticles (NPs) are omnipresent in our everyday life today. Many nanomaterials have been engineered for medical purposes. These purposes include therapy for pulmonary diseases. On other hand, people are endeavoring to develop nanomaterials for improvement or replacement of traditional therapies. On the other hand, nanoparticles, as foreign material in human bodies, are reported to have potential adverse effects on the lung, including oxidase stress, inflammation, fibrosis and genotoxicity. Further, these damages could induce pulmonary diseases and even injuries in other tissues. It seems that nanoparticles may exert two-sided effects. Toxic effects of nanomaterials should be considered when their use is developed for therapies. Hence this review will attempt to summarize the two-side roles of nanoparticles in both therapies for pulmonary diseases and initiation of lung diseases and even secondary diseases caused by lung injuries. Determinants of these effects such as physicochemical properties of nanoparticles will also be discussed. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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851 KiB  
Review
Nanoinformatics: Emerging Databases and Available Tools
by Suresh Panneerselvam and Sangdun Choi
Int. J. Mol. Sci. 2014, 15(5), 7158-7182; https://doi.org/10.3390/ijms15057158 - 25 Apr 2014
Cited by 68 | Viewed by 18300
Abstract
Nanotechnology has arisen as a key player in the field of nanomedicine. Although the use of engineered nanoparticles is rapidly increasing, safety assessment is also important for the beneficial use of new nanomaterials. Considering that the experimental assessment of new nanomaterials is costly [...] Read more.
Nanotechnology has arisen as a key player in the field of nanomedicine. Although the use of engineered nanoparticles is rapidly increasing, safety assessment is also important for the beneficial use of new nanomaterials. Considering that the experimental assessment of new nanomaterials is costly and laborious, in silico approaches hold promise. Several major challenges in nanotechnology indicate a need for nanoinformatics. New database initiatives such as ISA-TAB-Nano, caNanoLab, and Nanomaterial Registry will help in data sharing and developing data standards, and, as the amount of nanomaterials data grows, will provide a way to develop methods and tools specific to the nanolevel. In this review, we describe emerging databases and tools that should aid in the progress of nanotechnology research. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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377 KiB  
Review
Nanoparticle-Mediated Pulmonary Drug Delivery: A Review
by Mukta Paranjpe and Christel C. Müller-Goymann
Int. J. Mol. Sci. 2014, 15(4), 5852-5873; https://doi.org/10.3390/ijms15045852 - 8 Apr 2014
Cited by 354 | Viewed by 19261
Abstract
Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of [...] Read more.
Colloidal drug delivery systems have been extensively investigated as drug carriers for the application of different drugs via different routes of administration. Systems, such as solid lipid nanoparticles, polymeric nanoparticles and liposomes, have been investigated for a long time for the treatment of various lung diseases. The pulmonary route, owing to a noninvasive method of drug administration, for both local and systemic delivery of an active pharmaceutical ingredient (API) forms an ideal environment for APIs acting on pulmonary diseases and disorders. Additionally, this route offers many advantages, such as a high surface area with rapid absorption due to high vascularization and circumvention of the first pass effect. Aerosolization or inhalation of colloidal systems is currently being extensively studied and has huge potential for targeted drug delivery in the treatment of various diseases. Furthermore, the surfactant-associated proteins present at the interface enhance the effect of these formulations by decreasing the surface tension and allowing the maximum effect. The most challenging part of developing a colloidal system for nebulization is to maintain the critical physicochemical parameters for successful inhalation. The following review focuses on the current status of different colloidal systems available for the treatment of various lung disorders along with their characterization. Additionally, different in vitro, ex vivo and in vivo cell models developed for the testing of these systems with studies involving cell culture analysis are also discussed. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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1176 KiB  
Review
Toxicological Assessment of Inhaled Nanoparticles: Role of in Vivo, ex Vivo, in Vitro, and in Silico Studies
by Eleonore Fröhlich and Sharareh Salar-Behzadi
Int. J. Mol. Sci. 2014, 15(3), 4795-4822; https://doi.org/10.3390/ijms15034795 - 18 Mar 2014
Cited by 182 | Viewed by 17332
Abstract
The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the [...] Read more.
The alveolar epithelium of the lung is by far the most permeable epithelial barrier of the human body. The risk for adverse effects by inhaled nanoparticles (NPs) depends on their hazard (negative action on cells and organism) and on exposure (concentration in the inhaled air and pattern of deposition in the lung). With the development of advanced in vitro models, not only in vivo, but also cellular studies can be used for toxicological testing. Advanced in vitro studies use combinations of cells cultured in the air-liquid interface. These cultures are useful for particle uptake and mechanistic studies. Whole-body, nose-only, and lung-only exposures of animals could help to determine retention of NPs in the body. Both approaches also have their limitations; cellular studies cannot mimic the entire organism and data obtained by inhalation exposure of rodents have limitations due to differences in the respiratory system from that of humans. Simulation programs for lung deposition in humans could help to determine the relevance of the biological findings. Combination of biological data generated in different biological models and in silico modeling appears suitable for a realistic estimation of potential risks by inhalation exposure to NPs. Full article
(This article belongs to the Special Issue Nanotoxicology and Lung Diseases)
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