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© 2016 Elsevier B.V. The aim of this research was to assess biodistribution of orally administered poly(lactide-co-glycolide) acid nanoparticles (PLGA NPs) in rats and investigate the excretion of PLGA nanoparticles after administration has ended. The experiment was divided into 2 phases. In phase I, F344 rats were orally administered fluorescently tagged PLGA nanoparticles daily (3 mg/day) for 7 days, followed by a mass balance analysis which was performed on tissues of interest to determine NP biodistribution. In phase II, after 7 days of oral exposure, rats were no longer administered PLGA NPs, and amount of NPs excreted was measured each week for 3 weeks. At day seven, the last day of the nanoparticle exposure period, over half of the daily administered PLGA NPs were excreted. Among the nanoparticles recovered from the tissues, the majority was recovered in the intestines (23.4% daily dose), followed by the liver (11.4% daily dose), kidney (5.5% daily dose), spleen (2.5% daily dose), lung (2.0% daily dose), brain (1.0% daily dose), plasma (0.7% daily dose), and heart (0.2% daily dose), respectively. During phase II, the amount of NPs in the feces declined from the maximum excretion on day 7 (58.3% daily dose) to the minimum value on day 28 (6.7% daily dose), 3 weeks after NP administration ended. Little change in nanoparticle excretion was observed between day 21 and day 28, indicating the baseline had been reached. The findings are significant for understanding biodistribution and excretion of orally administered PLGA NPs and are relevant to their application in food, agriculture, and medicine.

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