Johns Hopkins Researchers Develop Improved Drug-Delivery Nanoparticles

Drug delivery is one of the hottest areas in medical device R&D, and nanotechnology is one of the hottest candidates for new drug-delivery vehicles. Adding to the heat, a team of bioengineers at Johns Hopkins Medicine (Baltimore) has designed nanoparticles for delivering a drug payload that can safely and predictably infiltrate into the brain, a difficult organ to treat.

After doctors perform surgery to remove a brain tumor, standard treatment protocols include the application of chemotherapy directly to the surgical site to kill any cells left behind. However, this method of preventing tumor recurrence is only moderately successful, in part because it is hard to administer a dose of chemotherapy high enough to sufficiently penetrate the tissue and low enough to be safe.

Conventional drug-delivery nanoparticles are made by entrapping drug molecules together with microscopic, stringlike molecules in a tight ball, which slowly breaks down when it comes into contact with water. However, such nanoparticles have not worked well because they stick to cells at the application site and tend to not migrate deeper into the tissue. "We are pleased to have found a way to prevent drug-embedded particles from sticking to their surroundings so that they can spread once they are in the brain," comments Justin Hanes, Lewis J. Ort Professor of Ophthalmology at Johns Hopkins.

Elizabeth Nance, a graduate student in chemical and biomolecular engineering at Johns Hopkins, and Johns Hopkins neurosurgeon Graeme Woodworth thought that drug penetration could be improved if drug-delivery nanoparticles interacted minimally with their surroundings. To test their supposition, Nance coated nanosized plastic beads of various sizes with poly(ethylene glycol), which has been shown to protect nanoparticles from the body's defense mechanisms. The team also reasoned that a dense layer of PEG might also make the beads more slippery.

The team then injected the coated beads into slices of rodent and human brain tissue. Compared with non-PEG-coated beads or beads with a less-dense PEG coating, they found that a dense coating of PEG allowed larger beads to penetrate the tissue. They then tested these beads in live rodent brains and found the same results.

Next, the researchers took biodegradable nanoparticles carrying the chemotherapy drug paclitaxel and coated them with PEG. As expected, nanoparticles without the PEG coating moved very little, while PEG-covered nanoparticles were better distributed.

"It's really exciting that we now have particles that can carry five times more drug, release it for three times as long and penetrate farther into the brain than before," Nance says. "The next step is to see if we can slow tumor growth or recurrence in rodents."