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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

Estimated bioavailability of 50 nm PS-NPs, expressed as a percentage of the administered dose (125 mg/kg bw), calculated by summing up the amounts of PS-NPs detected in all analysed organs, except the stomach- and intestinal walls and brain. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. Error bars show the standard error of mean (n = 5)
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Fig3: Estimated bioavailability of 50 nm PS-NPs, expressed as a percentage of the administered dose (125 mg/kg bw), calculated by summing up the amounts of PS-NPs detected in all analysed organs, except the stomach- and intestinal walls and brain. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. Error bars show the standard error of mean (n = 5)

Mentions: The overall bioavailability of PS-NPs was estimated by summing up the amounts of PS-NPs in all measured organs, except the stomach wall and intestinal walls, as PS-NPs present in these organs were most likely the result of direct absorption rather than from uptake from the blood, and except the brain, due to the selectivity of the blood–brain barrier. As shown in Fig. 3, the resulting amount of PS-NPs as a percentage of the administered dose was as low as 0.3 and 0.2 % for 50 nm (0) and (+) PS-NPs, respectively, while the (−M) and (−P) PS-NPs reached bioavailable levels of 1.5 and 1.7 %, respectively. Due to the large variability in the (−M) and (−P) groups, the higher estimated bioavailabilities of these PS-NPs are not significantly different (p = 0.2) from the estimated bioavailabilities of the (0) and (+) PS-NPs.Fig. 3


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)

Estimated bioavailability of 50 nm PS-NPs, expressed as a percentage of the administered dose (125 mg/kg bw), calculated by summing up the amounts of PS-NPs detected in all analysed organs, except the stomach- and intestinal walls and brain. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. Error bars show the standard error of mean (n = 5)
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4440892&req=5

Fig3: Estimated bioavailability of 50 nm PS-NPs, expressed as a percentage of the administered dose (125 mg/kg bw), calculated by summing up the amounts of PS-NPs detected in all analysed organs, except the stomach- and intestinal walls and brain. (0) neutral PS-NPs, (+) positively charged PS-NPs, (−M) and (−P) negatively charged PS-NPs from Magsphere and Polysciences, respectively. Error bars show the standard error of mean (n = 5)
Mentions: The overall bioavailability of PS-NPs was estimated by summing up the amounts of PS-NPs in all measured organs, except the stomach wall and intestinal walls, as PS-NPs present in these organs were most likely the result of direct absorption rather than from uptake from the blood, and except the brain, due to the selectivity of the blood–brain barrier. As shown in Fig. 3, the resulting amount of PS-NPs as a percentage of the administered dose was as low as 0.3 and 0.2 % for 50 nm (0) and (+) PS-NPs, respectively, while the (−M) and (−P) PS-NPs reached bioavailable levels of 1.5 and 1.7 %, respectively. Due to the large variability in the (−M) and (−P) groups, the higher estimated bioavailabilities of these PS-NPs are not significantly different (p = 0.2) from the estimated bioavailabilities of the (0) and (+) PS-NPs.Fig. 3

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