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Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats.

Walczak AP, Hendriksen PJ, Woutersen RA, van der Zande M, Undas AK, Helsdingen R, van den Berg HH, Rietjens IM, Bouwmeester H - J Nanopart Res (2015)

Bottom Line: In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential.This partly confirms our in vitro findings, where the same NPs translocated to the highest extent.The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %).

View Article: PubMed Central - PubMed

Affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands ; RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands.

ABSTRACT

The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.

No MeSH data available.


Related in: MedlinePlus

Whole-organ fluorescence following a single oral administration of 125 mg/kg bw PS-NPs. Pictures of kidney (a), small- (b) and large intestinal walls (c) at t = 6 h showing fluorescence under the illumination with wavelengths Ex/Em = 470/520 nm or 530/590 nm, for yellow-green (−P) PS-NPs and red (0, +, −M) PS-NPs, respectively. Control organs were collected from animals treated with only water. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. (Color figure online)
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Fig1: Whole-organ fluorescence following a single oral administration of 125 mg/kg bw PS-NPs. Pictures of kidney (a), small- (b) and large intestinal walls (c) at t = 6 h showing fluorescence under the illumination with wavelengths Ex/Em = 470/520 nm or 530/590 nm, for yellow-green (−P) PS-NPs and red (0, +, −M) PS-NPs, respectively. Control organs were collected from animals treated with only water. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. (Color figure online)

Mentions: Fluorescence of the collected blood and organs was determined. The concentration of the 50 nm (−P) PS-NPs was high enough for detection in the kidney and small- and large intestinal walls at the appropriate wavelength using fluorescent microscopy, and the concentrations of the 50 nm (0), (+) and (−M) PS-NPs were high enough for detection in the small- and large intestinal walls only (Fig. 1a–c). The fluorescence intensity could not be quantified reliably using whole organs. Therefore, fluorescence intensity was quantified using enzymatically digested organ homogenates, and PS-NP organ concentrations were determined based on standard calibration curves made in each organ. The PS-NP concentrations in the different organs are shown in Fig. 2. Each of the four types of PS-NPs induced a significant increase of fluorescence in at least one of the tested organs, indicating the passage of these PS-NPs through the intestinal wall. In animals exposed to 50 nm (−P) PS-NPs, the concentration of these PS-NPs was significantly increased in kidney (p < 0.05), spleen (p < 0.05), testis (p < 0.01), heart (p < 0.05), stomach wall (p < 0.000), small intestinal wall (p < 0.01) and large intestinal wall (p < 0.05). In animals exposed to 50 nm (+) PS-NPs, the concentration of these PS-NPs was significantly increased in kidney (p < 0.1), spleen (p < 0.01), testis (p < 0.01), lung (p < 0.1), heart (p < 0.1), stomach wall (p < 0.1), small intestinal wall (p < 0.01) and large intestinal wall (p < 0.01). The concentrations of 50 nm (0) and (−M) PS-NPs in the organs were considerably lower than those of 50 nm (−P) and (+) PS-NPs, and they reached significance only in few organs. In the animals exposed to 50 nm (0) PS-NPs, the concentration of these PS-NPs was significantly increased in spleen (p < 0.05), lung (p < 0.1), small intestinal wall (p < 0.05) and large intestinal wall (p < 0.01). The concentration of 50 nm (−M) PS-NPs was significantly increased in kidney (p < 0.05), stomach wall (p < 0.05), small intestinal wall (p < 0.05) and large intestinal wall (p < 0.05). No PS-NPs were detected in blood samples from any time point.Fig. 1


Bioavailability and biodistribution of differently charged polystyrene nanoparticles upon oral exposure in rats.

Walczak AP, Hendriksen PJ, Woutersen RA, van der Zande M, Undas AK, Helsdingen R, van den Berg HH, Rietjens IM, Bouwmeester H - J Nanopart Res (2015)

Whole-organ fluorescence following a single oral administration of 125 mg/kg bw PS-NPs. Pictures of kidney (a), small- (b) and large intestinal walls (c) at t = 6 h showing fluorescence under the illumination with wavelengths Ex/Em = 470/520 nm or 530/590 nm, for yellow-green (−P) PS-NPs and red (0, +, −M) PS-NPs, respectively. Control organs were collected from animals treated with only water. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. (Color figure online)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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Fig1: Whole-organ fluorescence following a single oral administration of 125 mg/kg bw PS-NPs. Pictures of kidney (a), small- (b) and large intestinal walls (c) at t = 6 h showing fluorescence under the illumination with wavelengths Ex/Em = 470/520 nm or 530/590 nm, for yellow-green (−P) PS-NPs and red (0, +, −M) PS-NPs, respectively. Control organs were collected from animals treated with only water. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. (Color figure online)
Mentions: Fluorescence of the collected blood and organs was determined. The concentration of the 50 nm (−P) PS-NPs was high enough for detection in the kidney and small- and large intestinal walls at the appropriate wavelength using fluorescent microscopy, and the concentrations of the 50 nm (0), (+) and (−M) PS-NPs were high enough for detection in the small- and large intestinal walls only (Fig. 1a–c). The fluorescence intensity could not be quantified reliably using whole organs. Therefore, fluorescence intensity was quantified using enzymatically digested organ homogenates, and PS-NP organ concentrations were determined based on standard calibration curves made in each organ. The PS-NP concentrations in the different organs are shown in Fig. 2. Each of the four types of PS-NPs induced a significant increase of fluorescence in at least one of the tested organs, indicating the passage of these PS-NPs through the intestinal wall. In animals exposed to 50 nm (−P) PS-NPs, the concentration of these PS-NPs was significantly increased in kidney (p < 0.05), spleen (p < 0.05), testis (p < 0.01), heart (p < 0.05), stomach wall (p < 0.000), small intestinal wall (p < 0.01) and large intestinal wall (p < 0.05). In animals exposed to 50 nm (+) PS-NPs, the concentration of these PS-NPs was significantly increased in kidney (p < 0.1), spleen (p < 0.01), testis (p < 0.01), lung (p < 0.1), heart (p < 0.1), stomach wall (p < 0.1), small intestinal wall (p < 0.01) and large intestinal wall (p < 0.01). The concentrations of 50 nm (0) and (−M) PS-NPs in the organs were considerably lower than those of 50 nm (−P) and (+) PS-NPs, and they reached significance only in few organs. In the animals exposed to 50 nm (0) PS-NPs, the concentration of these PS-NPs was significantly increased in spleen (p < 0.05), lung (p < 0.1), small intestinal wall (p < 0.05) and large intestinal wall (p < 0.01). The concentration of 50 nm (−M) PS-NPs was significantly increased in kidney (p < 0.05), stomach wall (p < 0.05), small intestinal wall (p < 0.05) and large intestinal wall (p < 0.05). No PS-NPs were detected in blood samples from any time point.Fig. 1

Bottom Line: In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential.This partly confirms our in vitro findings, where the same NPs translocated to the highest extent.The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %).

View Article: PubMed Central - PubMed

Affiliation: Division of Toxicology, Wageningen University, Tuinlaan 5, 6703 HE Wageningen, The Netherlands ; RIKILT Wageningen UR, P.O. Box 230, Akkermaalsbos 2, 6700 AE Wageningen, The Netherlands.

ABSTRACT

The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral, positive and negative) using a Caco-2/HT29-MTX in vitro intestinal translocation model. The NPs translocated in a surface charge-dependent manner. The present study aimed to validate this in vitro intestinal model by an in vivo study. For this, rats were orally exposed to a single dose of these polystyrene NPs and the uptake in organs was determined. A negatively charged NP was taken up more than other NPs, with the highest amounts in kidney (37.4 µg/g tissue), heart (52.8 µg/g tissue), stomach wall (98.3 µg/g tissue) and small intestinal wall (94.4 µg/g tissue). This partly confirms our in vitro findings, where the same NPs translocated to the highest extent. The estimated bioavailability of different types of NPs ranged from 0.2 to 1.7 % in vivo, which was much lower than in vitro (1.6-12.3 %). Therefore, the integrated in vitro model cannot be used for a direct prediction of the bioavailability of orally administered NPs. However, the model can be used for prioritizing NPs before further in vivo testing for risk assessment.

No MeSH data available.


Related in: MedlinePlus