Effect of Particle Size of Intratracheally Instilled Crystalline Silica on Pulmonary Inflammation

Kajiwara, Takayoshi; Ogami, Akira; Oyabu, Takako; Morimoto, Yasuo; Tanaka, Isamu

doi:10.1539/joh.49.88

Cited by 36 publications

(26 citation statements)

References 22 publications

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“…In human beings, toxicity becomes very important when aerodynamic diameter of the particles is 10 μm, which enables them to reach the pulmonary alveoli. In rats and mice, this value approximates 2 μm for intratracheally instilled silica (Wiessner et al, 1989; Takayoshi et al, 2007). The ROFA used in the present study was mainly composed of particles bigger than 10 μm (Avila et al, 2011), which would be less harmful than the smaller ones (Donaldson et al, 2001).…”

Section: Discussionmentioning

confidence: 91%

Time course of pulmonary burden in mice exposed to residual oil fly ash

et al. 2014

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Residual oil fly ash (ROFA) is a common pollutant in areas where oil is burned. This particulate matter (PM) with a broad distribution of particle diameters can be inhaled by human beings and putatively damage their respiratory system. Although some studies deal with cultured cells, animals, and even epidemiological issues, so far a comprehensive analysis of respiratory outcomes as a function of the time elapsed after exposure to a low dose of ROFA is wanted. Thus, we aimed to investigate the time course of mechanical, histological, and inflammatory lung changes, as well as neutrophils in the blood, in mice exposed to ROFA until 5 days after exposure. BALB/c mice (25 ± 5 g) were randomly divided into 7 groups and intranasally instilled with either 10 μL of sterile saline solution (0.9% NaCl, CTRL) or ROFA (0.2 μg in 10 μL of saline solution). Pulmonary mechanics, histology (normal and collapsed alveoli, mononuclear and polymorphonuclear cells, and ultrastructure), neutrophils (in blood and bronchoalveolar lavage fluid) were determined at 6 h in CTRL and at 6, 24, 48, 72, 96, and 120 h after ROFA exposure. ROFA contained metal elements, especially iron, polycyclic aromatic hydrocarbons (PAHs), and organochlorines. Lung resistive pressure augmented early (6 h) in the course of lung injury and other mechanical, histological and inflammatory parameters increased at 24 h, returning to control values at 120 h. Blood neutrophilia was present only at 24 and 48 h after exposure. Swelling of endothelial cells with adherent neutrophils was detected after ROFA instillation. No neutrophils were present in the lavage fluid. In conclusion, the exposure to ROFA, even in low doses, induced early changes in pulmonary mechanics, lung histology and accumulation of neutrophils in blood of mice that lasted for 4 days and disappeared spontaneously.

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Section: Discussionmentioning

confidence: 91%

Time course of pulmonary burden in mice exposed to residual oil fly ash

et al. 2014

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“…Particle size and surface area can play important roles in the response to inhaled particles, which is especially relevant for ultrafine or nano particles [1][2][3] . Our previous study using crystalline silica showed that even if the particles are of the same chemical composition, their biological effects vary depending on their particle size 4) . Hazard assessment of newly-generated respirable particles must therefore be conducted for such differences and various biomarker studies are currently being implemented to objectively and quantitatively assess the hazards of such substances [5][6][7][8][9][10][11][12][13][14] .…”

Section: Background and Objectivesmentioning

confidence: 99%

Analysis of Bronchoalveolar Lavage Fluid Adhering to Lung Surfactant

Kadoya¹,

Ogami²,

Morimoto³

et al. 2012

Ind Health

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Nickel oxide with two different particle sizes, micron size (NiO) and submicron size (nNiOm), as well as crystalline silica as a positive control and titanium dioxide as a negative control, were intratracheally instilled in rats and the phospholipid concentration and the protein concentration and surface tension of bronchoalveolar lavage fluid (BALF), which are used in surfactant assessment, were measured to see if they could be effective biomarkers in toxicity assessment. The results showed that the NiO instilled group showed no significant difference compared to the control group throughout the observation period. In contrast, a significant difference was found in the nNiOm instilled group compared to the control group throughout the observation period. Moreover, a significant difference was found in the crystalline silica instilled group for each measurement compared to the control group while for the titanium dioxide group, almost no significant difference was found. These results indicate that submicronsized particles of nickel oxide with smaller median diameters potentially have a stronger biological effect than micron size particles. They also indicate that screening can be done by measuring the phospholipid concentration and the protein concentration and surface tension of BALF.

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“…Moreover, the majority of studies investigating the fate of inhaled nanomaterials have been based on examining the lung clearance kinetics of the drug, rather than the polymer or polymer-drug conjugate. The critical issue here is that the safety of inhaled polymer-drug conjugates has also been called into question, based on widespread literature suggesting that nanomaterials, albeit nonbiodegradable/non-biocompatible nanoparticles, are 'toxic' in the lungs [16][17][18][19][20]. It is therefore important to understand the rate and mechanisms of polymer clearance from the lungs in order to design optimal dosing schedules that limit the long term retention of the polymer in the lungs and the potential for local adverse effects.…”

Section: Accepted M Manuscriptmentioning

confidence: 99%

“…It has been widely demonstrated that environmental pollutants including particulate material, inorganic/metal nanoparticles and non-biodegradable polymeric nanoparticles are capable of inducing inflammation, oxidative stress, cytotoxic and genotoxic effects in the lungs after inhalation [16][17][18][19][20]. In contrast, however, very few studies have been carried out to determine the immunological, inflammatory and toxicological potential of inhalable polymer drug conjugates or biodegradable polymers which have potential for pulmonary application.…”

Section: Current Opinion On the Future Of Inhalable Polymer-drug Conjmentioning

confidence: 99%

Polymer-drug conjugates as inhalable drug delivery systems: A review

Marasini

Haque

Kaminskas

2017

Current Opinion in Colloid & Interface Science

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Abstract:Accelerating interest by the pharmaceutical industry in the identification and development of less invasive routes of nanomedicine administration, coupled with defined efforts to improve the treatment of respiratory diseases through inhaled drug administration has fuelled growing interests in inhalable polymer-drug conjugates. Polymer-drug conjugates can alter the pharmacokinetics profile of the loaded drug after inhaled administration and enable the controlled and sustained exposure of the lungs to drugs when compared to the inhaled or oral administration of the drug alone. However, the major concern with the use of inhalable polymer-drug conjugates is their biocompatibility and long-term safety with the lungs, which is closely linked to their retention time in the lungs. A detailed understanding about the pharmacokinetics, lung disposition, clearance and safety of inhaled polymer-drug conjugates with significant translational potential is therefore required. This review therefore provides a comprehensive summary of the latest developments on several types of polymer-drug conjugates that are currently being explored as inhalable drug delivery systems. Finally, the current status and future perspective of the polymer-drug conjugates is also discussed with a focus on current knowledge gaps. Graphical abstract:

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Effect of Particle Size of Intratracheally Instilled Crystalline Silica on Pulmonary Inflammation

Cited by 36 publications

References 22 publications

Time course of pulmonary burden in mice exposed to residual oil fly ash

Time course of pulmonary burden in mice exposed to residual oil fly ash

Analysis of Bronchoalveolar Lavage Fluid Adhering to Lung Surfactant

Polymer-drug conjugates as inhalable drug delivery systems: A review

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