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A new study could allay some of the fears about health and safety issues relating to carbon nanotubes and open the door for exploring the use of such nanomaterials in the human body.
In the study, mice were intravenously administered functionalized, water-soluble carbon nanotubes, either single-walled or multiwalled. Electron microscopy analysis revealed that both types of nanotubes are excreted intact in urine.
The work was carried out at the Centre for Drug Delivery Research at the University of London's School of Pharmacy and was led by Kostas Kostarelos, deputy head of the center, in collaboration with organic chemists Alberto Bianco at the CNRS Institute of Molecular & Cellular Biology, in Strasbourg, France, and Maurizio Prato of the University of Trieste, in Italy (Proc. Natl. Acad. Sci. USA, published online, dx.doi.org/10.1073/pnas.0509009103).
"This is the first time carbon nanotubes have been administered intravenously and fundamental pharmacokinetic parameters have been obtained," Kostarelos tells C&EN. "It is also the first report showing blood clearance and urine excretion of the nanotubes."
From the point of view of biomedical applications, identifying the pharmacological limitations and advantages of such nanostructures is imperative for any kind of therapeutic or diagnostic application that involves administering or implanting carbon nanotubes in patients, he notes.
The researchers solubilized the nanotubes by functionalizing them with hydrophilic amino groups, using 1,3-dipolar cycloaddition of azomethine ylides. They then covalently linked the amino groups to a diethylenetriaminepentaacetic chelating agent. The radioactive isotope indium-111 complexed with the agent was used for imaging the nanotubes.
Radioactivity tracing showed that the intravenously administered soluble single-walled nanotubes were not retained in organs such as the heart, liver, and spleen. The team did not investigate the tissue biodistribution and blood clearance rates of the multiwalled tubes but carried out urine excretion studies on both types of tubes using transmission electron microscopy.
Research over the past couple of years has shown that, when inhaled, carbon nanotubes can accumulate in lungs and cause inflammation.
The new study has dismissed many of the worries of using nanotubes in therapeutics, showing that solubilized nanotubes "flush through [mice] without being retained in organs," says carbon nanotube expert Pulickel M. Ajayan, professor of engineering at Rensselaer Polytechnic Institute, Troy, N.Y. "This certainly removes the shroud that has made many people nervous about using nanotubes, especially for medical applications."
The study is "the first to show the viability of functionalized nanotubes as candidates for the development of new, biocompatible therapeutic strategies," comments Martin Philbert, professor of toxicology at the University of Michigan, Ann Arbor. "It remains to be seen whether or not longer term issues of toxicity will mitigate the usefulness of this exciting approach to drug delivery."
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