Little is known about the uptake, biodistribution, and biological responses of nanoparticles (NPs) and their toxicity in developing animals. Here, male and female juvenile Sprague–Dawley rats received four consecutive daily doses of 10 mg/kg Al2O3NP (diameter: 24 nm [transmission electron microscope], hydrodynamic diameter: 148 nm) or vehicle control (water) by gavage between postnatal days (PNDs) 17–20. Basic neurobehavioral and cardiac assessments were performed on PND 20. Animals were sacrificed on PND 21, and selected tissues were collected, weighed, and processed for histopathology or neurotransmitter analysis. The biodistribution of Al2O3NP in tissue sections of the intestine, liver, spleen, kidney, and lymph nodes were evaluated using enhanced dark‐field microscopy (EDM) and hyperspectral imaging (HSI). Liver‐to‐body weight ratio was significantly increased for male pups administered Al2O3NP compared with control. HSI suggested that Al2O3NP was more abundant in the duodenum and ileum tissue of the female pups compared with the male pups, whereas the abundance of NP was similar for males and females in the other tissues. The abundance of NP was higher in the liver compared with spleen, lymph nodes, and kidney. Homovanillic acid and norepinephrine concentrations in brain were significantly decreased following Al2O3NP administration in female and male pups, whereas 5‐hydroxyindoleacetic acid was significantly increased in male pups. EDM/HSI indicates intestinal uptake of Al2O3NP following oral administration. Al2O3NP altered neurotransmitter/metabolite concentrations in juvenile rats' brain tissues. Together, these data suggest that orally administered Al2O3NP interferes with the brain biochemistry in both female and male pups.
- Award ID(s):
- 1742339
- NSF-PAR ID:
- 10228273
- Date Published:
- Journal Name:
- Recent Patents on Drug Delivery & Formulation
- Volume:
- 14
- Issue:
- 3
- ISSN:
- 1872-2113
- Page Range / eLocation ID:
- 233 to 241
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.2174/1872211314999201117130123
