Site-directed drug delivery
Every drug carries a risk. Compounding that fact, drugs delivered by conventional methods
can diffuse to unwanted areas. For that reason, Andre G. Skirtach and colleagues
have developed a laser-based method that uses microcapsules for targeted drug delivery.
The site-directivity of microcapsules is particularly
important for targeting cancer cells because cancer drugs are often very harmful
to healthy somatic cells, Skirtach said. The method allows the release of the drug
to be delayed until a laser beam hits the microcapsule. The only other means of
directly delivering a drug to a cell is injection, which probably would damage the
To test the method, the researchers
packaged fluorescently tagged dextran in microcapsules. The tag allowed them to
view the release of the dextran. They compared Alexa Fluor 488 with fluoroscein
isothiocyanate and decided to use the former because it was bright, did not fluctuate
over a pH range and did not exhibit photobleaching.
The image on the left shows a microcapsule inside a cell, using
superimposed fluorescence and transmission modes. The image on the right is similar,
except that the laser beam has hit the cell. © Angewandte Chemie 2006.
The template for microcapsule preparation
was composed of silica. According to Skirtach, silica is advantageous because it
can be removed before encapsulation. The researchers added layers of polystyrene
sulfonate and (poly)diallyldimethylammonium chloride.
Next, they used a heat-shrinking method
— developed by fellow lab member Karen Köhler — that allowed
the material to be encapsulated, enabling them to control the thickness, size and
stiffness without deforming the capsule. Increasing the thickness and stiffness
was necessary because the forces upon uptake can cause warping.
Finally, the scientists deposited gold
or silver nanoparticles on the microcapsules to serve as the absorbent material
for the laser. Their early studies were conducted with silver nanoparticles, but
they switched to gold because of its surface chemistry control.
The researchers triggered the release
of the dextran in living cells with a diode laser that they constructed using Sanyo
parts. They operated the laser in continuous-wave mode and opened the shutter only
for brief pulses, which minimized cell damage. They used an 830-nm emission, one
of the biologically safest wavelengths, and recorded the results using a standard
Besides its utility for drug delivery,
the technique could help researchers and clinicians measure the uptake of medicine.
According to Skirtach, the current method of measurement involves using a confocal
microscope, which is more laborious because it requires multiple scans in the Z
plane. The resulting confocal images are ambiguous, he said.
Although the scientists tested their
system using dextran, they plan on performing future experiments with other compounds
that have more relevance to the pharmaceutical industry.
This method was developed by researchers
at Max Planck Institute for Colloids and Interfaces in Golm and at Ludwig Maximilians
University in Munich, both in Germany, and at Queen Mary University in London.
Angewandte Chemie, July 2006, pp. 4728-4733.
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