BALTIMORE—Researchers at Johns Hopkins University may have discovered the next generation of drug and cell therapy delivery devices—dust-sized, porous, metallic 3-D microcontainers that have the potential to carry everything from pain medication to cell therapy. The findings of the team were published in the December issue of the journal Biomedical Microdevices.
"These [microcontainers] are not biodegradable so we wouldn't expect them to replace applications where the delivery systems degrade in the body," says David Gracias, assistant professor in the Department of Chemical and Biomolecular Engineering in the Whiting School of Engineering at Johns Hopkins, who led the lab team fabricating the tiny boxes. "But they are chemically and mechanically stable and that would make them applicable for cell encapsulation therapies. We can also control the porosity on the faces of the cubes very well, which controls both the diffusion and immune response to any enclosed therapies."
To make the self-assembling containers, Gracias and his colleagues employ techniques used to make microelectronic circuits—thin film deposition, photolithography and electrodeposition—to make a flat pattern of six squares, in a shape resembling a cross. Each square, made of copper or nickel, has small openings etched into it, so that it eventually will allow medicine or therapeutic cells to pass through.
The researchers use metallic solder to form hinges along the edges between adjoining squares. When the flat shapes are heated briefly in a lab solution, the metallic hinges melt. High surface tension in the liquified solder pulls each pair of adjoining squares together like a swinging door. When cooled, the solder hardens again and the containers retain their box-like shape. The researchers also demonstrated the ability to insert into the cubes a suspension containing microbeads commonly used in cell therapy.
Because the boxes are metallic, Gracias says, they can be tracked easily within the body using technology such as MRI. Further, the researchers have shown the boxes have the ability to release their contents via electromagnetic agitation. "We see potential for these to be used in pain therapy, so that when a patient feels pain, they can hit a button, like a remote control, that will allow them to release medication," says Gracias.
While the containers undergo toxicity studies, the Hopkins researchers will be working on refining the fabrication techniques and on reducing the pore sizes on the boxes.
"Currently, we are making them with pores on the microscale, but for some potential uses, we know we need to create pores on the nanoscale," says Gracias.
Controlling the pore size on the boxes is important depending on the type of therapy these microcontainers may target. "If we want to prevent the body's immune response to these therapies, we need to prevent things from entering them," Gracias explains. "So we know the size of white blood cells and the sizes of pores to prevent them from entering. For insulin therapy, we know that to prevent the cytokines from entering, the pores need to be between 15 and 20 nanometers and we still have some work to do to create pores that size."
