Pushing Particles with PEG

Despite recent breakthroughs in cancer research, brain tumors remain difficult to treat. Drugs are not always effective as the brain is very adept at removing foreign molecules, and surgery can be even more problematic.

Current treatment typically removes as much of the tumor as possible and then places a chemotherapy dispensing implant near the site to administer drugs post operatively. Theoretically, this prevents tumors from growing back.

However, this is not always successful as the dispensed drug is often minimally water-soluble and thus cannot penetrate into the brain. Working with other researchers from Yale and Cornell, Professor Mark Saltzman has now developed a promising new method of treatment that could evade this problem.

The bioengineers bonded polyethylene glycol (PEG), a water-soluble polymer, to the chemotherapy drug camptothecin, finding that the altered drug was able to travel considerably farther in a rat brain than was possible for the drug alone.

PEG was chosen after the team tried to bond several other molecules to a chemotherapy drug. They started with dextran, which has similar properties to PEG, but the trials were not as successful. Dr. Saltzman and his colleagues chose PEG since it has been used previously to modify proteins, increasing the time that they are able to circulate.

This type of drug conjugation is possible because PEG increases the water solubility of the drug, which is then better able to penetrate into the brain. PEG’s high molecular weight also makes it more difficult for the brain to clear the drug-PEG conjugate, as opposed to the drug alone. This allows the drug to remain in the brain for a longer period of time.

Saltzman now hopes to expand trials of PEG-bonded chemotherapy drugs to larger animals and eventually to humans. These drugs also have possible applications to other localized cancers, such as prostate or ovarian cancer.

Another promising drug delivery system implants virus-sized nanoparticles in the tumor. These nanoparticles function like web to entangle multiple chemotherapy drugs, allowing several to work in synchrony. The nanoparticles would also prevent the drugs from getting swept away by the brain’s clearing mechanisms thereby allowing them to act longer on the tumor.

Hopefully, these novel treatment mechanisms will allow doctors to more effectively treat and cure brain tumors in the future.