biostudies-literatureJones GNational Heart, Lung, and Blood InstituteNHLBI NIH HHS1649-1662https://www.ebi.ac.uk/biostudies/studies/S-EPMC9869290biostudies-literatureUnknown17(22)<b>Aim:</b> To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. <b>Materials & methods:</b> The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. <b>Results:</b> DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). <b>Conclusion:</b> DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.Nanomedicine (London, England)Pharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats.PMC9869290HL143020R01 HL143020Kang HZeng LChoi HSJones GPark SHKim JStiles WRfalsePharmacokinetics and tissue distribution of deferoxamine-based nanochelator in rats.<b>Aim:</b> To characterize the pharmacokinetics of deferoxamine-conjugated nanoparticles (DFO-NPs), a novel nanochelator for removing excess iron. <b>Materials & methods:</b> The pharmacokinetics of DFO-NPs were evaluated in Sprague-Dawley rats at three doses (3.3, 10 and 30 μmol/kg) after intravenous and subcutaneous administration. <b>Results:</b> DFO-NPs exhibited a biphasic concentration-time profile after intravenous administration with a short terminal half-life (2.0-3.2 h), dose-dependent clearance (0.111-0.179 l/h/kg), minimal tissue distribution and exclusive renal excretion with a possible saturable reabsorption mechanism. DFO-NPs after subcutaneous administration exhibited absorption-rate-limited kinetics with a prolonged half-life (5.7-10.1 h) and favorable bioavailability (47-107%). <b>Conclusion:</b> DFO-NPs exhibit nonlinear pharmacokinetics with increasing dose, and subcutaneous administration substantially improves drug exposure, thereby making it a clinically viable administration route for iron chelation.2022-01-01T00:00:00Z2022 Sep2025-04-04T22:56:19.717Z2025-04-04T22:56:19.717ZS-EPMC98692903654723110.2217/nnm-2022-0159