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Improved nanoparticles deliver drugs into brain
Date:9/11/2012

anoparticles historically have not worked very well because they stick to cells at the application site and tend to not migrate deeper into the tissue.

Elizabeth Nance, a graduate student in chemical and biomolecular engineering at Hopkins, and Hopkins neurosurgeon Graeme Woodworth, M.D., suspected that drug penetration might be improved if drug-delivery nanoparticles interacted minimally with their surroundings. Nance first coated nano-sized plastic beads of various sizes with a clinically tested molecule called PEG, or poly(ethylene glycol), that had been shown by others to protect nanoparticles from the body's defense mechanisms. The team 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. They first labeled the beads with glowing tags that enabled them to see the beads as they moved through the tissue. Compared to 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, even those beads that were nearly twice the size previously thought to be the maximum possible for penetration within the brain. They then tested these beads in live rodent brains and found the same results.

The researchers then took biodegradable nanoparticles carrying the chemotherapy drug paclitaxel and coated them with PEG. As expected, in rat brain tissue, nanoparticles without the PEG coating moved very little, while PEG-covered nanoparticles distributed themselves quite well.

"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," says Nance. "The next step is to see if we can slow tumor growth or recurrence in rodents." Woodworth added that the team "also wants to optimize the particles and pair them with drugs to treat other brain diseases
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Contact: Cathy Kolf
ckolf@jhmi.edu
443-287-2251
Johns Hopkins Medicine
Source:Eurekalert  

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