3D-printed sponge could reduce side effects of chemotherapy

CHEMICAL engineers at the University of California (UC), Berkeley, US, have developed a 3D-printed ‘drug sponge’ which could help reduce the side effects of chemotherapy by absorbing excess drugs.

Most anti-cancer drugs are poisonous, and chemotherapy can cause major side effects, such as nausea, vomiting, diarrhoea, and suppression of the immune system. These effects can be minimised by targeting drugs to the site of the tumour using a catheter for delivery (intra-arterial chemotherapy), but typically more than half of the drug can still escape the target organ and potentially poison other organs in the body.

Hee Jeung Oh (University of California, Berkeley) and ACS Central Science

The group at UC Berkley developed a drug sponge which in pig veins was able to absorb an average of 64% of the doxorubicin injected into the blood, upstream of the device. Doxorubicin is a widely-used and effective chemotherapy drug that has significant toxic side effects. No immediate adverse effects were observed.

The drug sponge is a 3D-printed cylinder with a polymer coating. The polymer has outer portions which allow it to anchor to the cylindrical support, and a middle portion that contains polystyrenesulfonate which binds the doxorubicin.

Nitash Balsara, a Professor of Chemical and Biomolecular Engineering at UC Berkeley, told a university reporter that the cylinder is 3D printed so that it can fit precisely into a vein that carries blood out of the target organ. 3D printing the cylinder could also allow it to be customised to fit an individual patient’s veins. This is important as a poor fit would allow the drug to flow past the cylinder without interacting with the absorbent.

The device could be deployed for absorption during chemotherapy. By using a wire to move it through the bloodstream surgeons could place the sponge like a stent, Balsara explained. The sponge could then be left for the duration of chemotherapy.

Steven Hetts, a professor at UC San Francisco (UCSF) and Chief of Interventional Neuroradiology at the UCSF Mission Bay Hospitals, was the one to approach Balsara in search of a way to remove drugs from the bloodstream. He told a UC Berkeley reporter that they are developing the drug sponge around liver cancer, but that it could be used in the treatment of other tumours. It could be used to reduce side effects, or even to allow doctors to use higher drug doses for the treatment of less responsive tumours.

The drug sponge could also be used to capture other drugs, or to treat other diseases confined to an organ. For example, the sponge could be used to absorb high-powered antibiotics that are toxic to kidneys but required to kill a pathogen. “We think this is a generally applicable concept,” said Hetts.

In addition, Hetts claimed that this technique is superior to another liver drug removal technique currently undergoing testing. The other method requires major endovascular surgery to block the outputs from the liver with balloons and divert outflowing blood to an external dialysis machine. The machine removes the drug, and the blood is returned to the body.

“There is a lot of opportunity to develop less-invasive devices that will bind up the drug in a gentler manner,” Hetts said.

However, although the drug sponge represents a step forward in minimising toxic side effects of chemotherapy, its true promise won’t be known until human trials have been carried out.

Currently the group is doing experiments to determine how much drug is absorbed when the device is used in healthy pigs, but Hetts said that “extensive animal testing is not the next path; the next path is getting conditional approval from the FDA to do first-in-human studies”. Human studies in cancer patients will provide more realistic results, he explained. Hetts imagines that human trials could begin in “a couple of years”. “Because it is a temporary device, there is a lower bar in terms of approval by the FDA,” Hetts added. “I think this type of chemofilter is one of the shortest pathways to patients.”

This work was supported by a grant from the National Institute of Health.

ACS Central Science: http://doi.org/czwj