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'Spiking' patients: Technique could improve drug delivery

Nanofiber Needles.JPG

This image shows carbon nanofiber "needles" embedded in an elastic silicone membrane. (Anatoli Melechko, North Carolina State University)

It may look like a medieval torture instrument, but a device made of carbon nanofiber "spikes" embedded into a patch of flexible silicon could provide a new way of delivering drugs or snippets of DNA into cells.

Researchers at North Carolina University say their novel cellular-delivery mechanism could inject medicine directly into blood vessels or the walls of soft tissue. It could even potentially bypass the brain-blood barrier.

That barrier refers to the boundary between capillaries and the rest of the brain. Cells surrounding these capillaries protect the brain's environment by severely restricting what substances can enter into the nervous system from the blood.

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In the future, doctors could take the spiky material, fashion it into a small, prickly balloon, and insert it into the body. Once the balloon reaches the desired location, a technician makes the balloon inflate like a puffer fish, thereby piercing the cell membrane and delivering its payload. After doing its job, the balloon can be deflated and removed.

Carbon nanofibers are made of stacked domes intereconnected carbon atoms called graphene. They are the choice material for these spikes because the nanofibers are durable, easy to modify and grow vertically in stalks without need of support. To make the spikes sturdier, researchers added a silicon-nitrogen coating, which slopes up to a peak on either side, making the fibers look like teeth.

Best of all, the spikes won’t leave a gaping hole in a blood vessel. “Previous work has demonstrated that the cell membrane can effectively reseal following nanofiber penetration,” explained Tim McKnight from the Oak Ridge National Laboratory, who worked with the NCU team. 

Scientists have discussed the nanofiber balloon idea for some time, but implementing it has posed a challenge. “[Researchers] have been thinking along these lines for several years,” McKnight said. Unfortunately, the materials conventionally used for growing nanofibers "are not conducive to tissue integration due to significant mismatch between the rigidity of the substrate [materials] and the softness of tissue.”

To get around this obstacle, the team first grew the fibers on aluminum, and then coated the area with a fine layer of silicone called PDMS (a main component in Silly Putty). Once the silicone hardened, researchers disintegrated the aluminum by soaking it in potassium hydroxide, thus leaving a flexible substrate with the sharp fibers sticking out.

Lastly, the researchers tested the material on a line of brain endothelial cells, the gatekeeper cells of the brain-blood barrier, to see if it would impale the cells and transfer the snippets of DNA they had added. “We demonstrated delivery and expression of a transgene into endothelial cells,” which made the cells glow, McKnight explained.

The researchers also noted that the straightforward fabrication process and the inexpensiveness of aluminum further bolster the material’s potential in drug delivery.   

The research was detailed online on  January 2 in the journal ACS Applied Materials and Interfaces.

 

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