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Targeted drug delivery of antifungal agents has been demonstrated by French and Italian researchers using carbon nanotubes. NMR and transmission electron microscopy reveal the structures involved. Classical drug delivery is fairly straightforward: the patient either eats, inhales, or injects a drug. But, usually that's as targeted as the delivery gets from there on in the compound is left to its own devices. However, targeting specific cells in the body is crucial to creating more effective treatments and avoiding side effects. Now, a French and Italian team has successfully used carbon nanotubes as transport agents for antifungal agents. In addition, the team has developed a strategy for attaching a second agent or marker to the nanotubes in a controlled fashion. Alberto Bianco of the CNRS (Centre National de la Recherche Scientifique) of Strasbourg describes the carbon nanotube, as able to "drill through cell membranes like tiny needles, without damaging the cell." By attaching a therapeutic protein or nucleic acid to the nanotubes, the nanotube can transport these compounds directly into the cell. Bianco and colleagues at the CNRS and the University of Trieste wanted to determine if this concept could also be extended to small pharmaceutical molecules such as antimycotics and cancer drugs. They were particularly intrigued by the idea of attaching not one, but two different "passengers". Two agents would allow combination therapies to be undertaken with one agent the drug, and a second acting as a marker. This can be done by attaching molecules that are recognised by specific receptors at the cell surface, explains Bianco. To attach their agents, the researchers created two distinct anchor sites on the nanotubes, equipped with protective "caps", on the tips and sides walls of the tubes. They removed the first type of ?cap? and attached one kind of molecule, then removed the second type of cap and attached the other type of molecule. Using this strategy, they could load nanotubes with the antimycotic amphotericin B and a fluorescent marker compound. Bianco and his colleagues discovered that the toxic side effects typical of treatment with amphotericin B are reduced greatly by using nanotubes to deliver the drug. Moreover, its efficacy rises, perhaps as a result of increased water solubility and reduced agglomeration of the compound. "Our approach could help amphotericin B become more widely used against chronic fungal infections," says Bianco. The next step is to develop a guiding molecule that could also be attached to the nanotubes to allow them to target only certain types of cells, such as tumour cells. "Ours are preliminary results and it is too early to anticipate clinical trials," Bianco told spectroscopyNOW, "We are currently thinking of how to add anticancer drugs and target cancer cells by linking, together with the drug, a molecule that is recognised by receptors on the surface of cancer cells."
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Spiked - a cell and a fluorescent nanotube (Credit: Wu et al.)
Cells spiked by nanotube needles fluorescing (Credit: Wu et al. / Wiley)
Alberto Bianco |
