title: In vitro and in vivo evaluation of a novel ferrocyanide functionalized nanopourous silica decorporation agent for cesium in rats.
abstract: Novel decorporation agents are being developed to protect against radiological terrorist attacks. These sorbents, known as the self-assembled monolayer on mesoporous supports (SAMMS), are hybrid materials where differing organic moieties are grafted onto mesoporous silica (SiO(2)). In vitro experiments focused on the evaluation and optimization of SAMMS for capturing radiocesium ((137)Cs); therefore, based on these studies, a ferrocyanide copper (FC-Cu-EDA)-SAMMS was advanced for in vivo evaluation. In vivo experiments were conducted comparing the performance of the SAMMS vs. insoluble Prussian blue. Groups of jugular cannulated rats (4/treatment) were evaluated. Animals in Group I were administered (137)Cs chloride (approximately 40 microg kg(-1)) by intravenous (i.v.) injection or oral gavage; Group II animals were administered pre-bound (137)Cs-SAMMS or sequential Cs chloride + SAMMS (approximately 61 ng kg(-1)) by oral gavage; and Group III was orally administered (137)Cs chloride (approximately 61 ng kg(-1)) followed by either 0.1 g of SAMMS or Prussian blue. Following dosing, the rats were maintained in metabolism cages for 72 h and blood, urine, and fecal samples were collected for (137)Cs analysis (gamma counting). Rats were then humanely euthanized, and selected tissues analyzed. Orally administered (137)Cs chloride was rapidly and well absorbed (approximately 100% relative to i.v. dose), and the pharmacokinetics (blood, urine, feces, and tissues) were very comparable to the i.v. dose group. For both exposures the urine and feces accounted for 20 and 3% of the dose, respectively. The prebound (137)Cs-SAMMS was retained primarily within the feces (72% of the dose), with approximately 1.4% detected in the urine, suggesting that the (137)Cs remained tightly bound to SAMMS. SAMMS and Prussian blue both effectively captured available (137)Cs in the gut with feces accounting for 80-88% of the administered dose, while less than 2% was detected in the urine. This study suggests that the functionalized SAMMS outperforms Prussian blue in vitro at low pH, but demonstrates comparable in vivo sequestration efficacy at low exposure concentrations. The comparable response may be the result of the low (137)Cs chloride dose and high sorbent dosage that was utilized. Future studies are planned to optimize the performance of SAMMS in vivo over a broader range of doses and conditions.
authors.affiliation: Pacific Northwest National Laboratory, 902 Battelle Blvd., PO Box 999, Richland, WA 99352, USA. charles.timchalk@pnl.gov
authors.forename: Charles
authors.initials: C
authors.lastname: Timchalk
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Creim
authors.forename: Vichaya
authors.initials: V
authors.lastname: Sukwarotwat
authors.forename: Robert
authors.initials: R
authors.lastname: Wiacek
authors.forename: R Shane
authors.initials: RS
authors.lastname: Addleman
authors.forename: Glen E
authors.initials: GE
authors.lastname: Fryxell
authors.forename: Wassana
authors.initials: W
authors.lastname: Yantasee
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002586:Cesium / Q000097:blood / Q000302:isolation & purification* / Q000378:metabolism / Q000652:urine; D002712:Chlorides; D003666:Decontamination / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005243:Feces / Q000737:chemistry; D005295:Ferrocyanides / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D008297:Male; D053758:Nanoparticles; D016062:Porosity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D002712:Chlorides; D005295:Ferrocyanides; D002586:Cesium; D012822:Silicon Dioxide; C028019:cesium chloride