Tissue biodistribution and blood clearance rates of intravenously administered carbon nanotube radiotracers.
Carbon nanotubes (CNT) are intensively being developed for biomedical applications including drug and gene delivery. Although all possible clinical applications will require compatibility of CNT with the biological milieu, their in vivo capabilities and limitations have not yet been explored. In this work, water-soluble, single-walled CNT (SWNT) have been functionalized with the chelating molecule diethylentriaminepentaacetic (DTPA) and labeled with indium ((111)In) for imaging purposes. Intravenous (i.v.) administration of these functionalized SWNT (f-SWNT) followed by radioactivity tracing using gamma scintigraphy indicated that f-SWNT are not retained in any of the reticuloendothelial system organs (liver or spleen) and are rapidly cleared from systemic blood circulation through the renal excretion route. The observed rapid blood clearance and half-life (3 h) of f-SWNT has major implications for all potential clinical uses of CNT. Moreover, urine excretion studies using both f-SWNT and functionalized multiwalled CNT followed by electron microscopy analysis of urine samples revealed that both types of nanotubes were excreted as intact nanotubes. This work describes the pharmacokinetic parameters of i.v. administered functionalized CNT relevant for various therapeutic and diagnostic applications.
Singh
Ravi
R
Centre for Drug Delivery Research, School of Pharmacy, University of London, UK.
Pantarotto
Davide
D
Lacerda
Lara
L
Pastorin
Giorgia
G
Klumpp
Cédric
C
Prato
Maurizio
M
Bianco
Alberto
A
Kostarelos
Kostas
K
D000818:Animals; D005260:Female; D006207:Half-Life; D007205:Indium Radioisotopes; D007275:Injections, Intravenous; D051379:Mice; D008807:Mice, Inbred BALB C; D046529:Microscopy, Electron, Transmission; D015394:Molecular Structure; D037742:Nanotubes, Carbon / Q000032:analysis*; D004369:Pentetic Acid; D014018:Tissue Distribution
D007205:Indium Radioisotopes; D037742:Nanotubes, Carbon; D004369:Pentetic Acid