Site-directed drug delivery

David Shenkenberg

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 cell membrane.

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 CCD camera.

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.