title: Energy dispersive X-ray analysis of titanium dioxide nanoparticle distribution after intravenous and subcutaneous injection in mice.
abstract: In an effort to understand the disposition and toxicokinetics of nanoscale materials, we used EDS (energy dispersive X-ray spectroscopy) to detect and map the distribution of titanium dioxide (TiO2) in tissue sections from mice following either subcutaneous (s.c.) or intravenous (i.v.) injection. TiO2 nanoparticles were administered at a dose of 560 mg/kg (i.v.) or 5600 mg/kg (s.c.) to Balb/c female mice on two consecutive days. Tissues (liver, kidney, lung, heart, spleen, and brain) were examined by light microscopy, TEM (transmission electron microscopy), SEM (scanning electron microscopy), and EDS following necropsy one day after treatment. Particle agglomerates were detected by light microscopy in all tissues examined, EDS microanalysis was used to confirm that these tissues contained elemental titanium and oxygen. The TEM micrographs and EDS spectra of the aggregates were compared with in vitro measurements of TiO2 nanoparticle injection solution (i.e., in water). The nanoparticles were also characterized using dynamic light scattering in water, 10 mM NaCl, and phosphate buffered saline (PBS). In low ionic strength solvents (water and 10 mM NaCl), the TiO2 particles had average hydrodynamic diameters ranging from 114-122 nm. In PBS, however, the average diameter increases to 1-2 microm, likely due to aggregation analogous to that observed in tissue by TEM and EDS. This investigation demonstrates the suitability of energy dispersive X-ray spectroscopy (EDS) for detection of nanoparticle aggregates in tissues and shows that disposition of TiO2 nanoparticles depends on the route of administration (i.v. or s.c.).
authors.affiliation: Nanotechnology Characterization Laboratory, SAIC-Frederick Inc., NCI-Frederick, Frederick, Maryland 21702, USA.
authors.forename: Anil
authors.initials: A
authors.lastname: Patri
authors.forename: Thomas
authors.initials: T
authors.lastname: Umbreit
authors.forename: J
authors.initials: J
authors.lastname: Zheng
authors.forename: K
authors.initials: K
authors.lastname: Nagashima
authors.forename: Peter
authors.initials: P
authors.lastname: Goering
authors.forename: Sabine
authors.initials: S
authors.lastname: Francke-Carroll
authors.forename: Edward
authors.initials: E
authors.lastname: Gordon
authors.forename: James
authors.initials: J
authors.lastname: Weaver
authors.forename: Terry
authors.initials: T
authors.lastname: Miller
authors.forename: Nakissa
authors.initials: N
authors.lastname: Sadrieh
authors.forename: Scott
authors.initials: S
authors.lastname: McNeil
authors.forename: Mel
authors.initials: M
authors.lastname: Stratmeyer
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000032:analysis / Q000493:pharmacokinetics; D005260:Female; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008099:Liver / Q000737:chemistry / Q000648:ultrastructure; D053768:Metal Nanoparticles / Q000008:administration & dosage / Q000032:analysis* / Q000648:ultrastructure; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D010316:Particle Size; D053838:Scattering, Small Angle; D013052:Spectrometry, X-Ray Emission; D014018:Tissue Distribution; D014025:Titanium / Q000008:administration & dosage / Q000032:analysis* / Q000493:pharmacokinetics
chemical_list: D001672:Biocompatible Materials; C009495:titanium dioxide; D014025:Titanium