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Posted: Sep 17, 2012
Coated nanoparticles move easily into brain tissue
(Nanowerk News) Johns Hopkins researchers report they are one step closer to having a drug-delivery system flexible enough to overcome some key challenges posed by brain cancer and perhaps other maladies affecting that organ. In a report published online Aug. 29 in Science Translational Medicine ("A Dense Poly(Ethylene Glycol) Coating Improves Penetration of Large Polymeric Nanoparticles Within Brain Tissue "), the Johns Hopkins team says its bioengineers have designed nanoparticles that can safely and predictably infiltrate deep into the brain when tested in rodent and human 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,” said Justin Hanes, Lewis J. Ort Professor of Ophthalmology and project leader in the Johns Hopkins Center of Cancer Nanotechnology Excellence.
Real-time imaging of nanoparticles (green) coated with polyethylene-glycol (PEG), a hydrophilic, non-toxic polymer, penetrate within normal rodent brain. Without the PEG coating, negatively charged, hydrophobic particles (red) of a similar size do not penetrate. (Image by Elizabeth Nance, Kurt Sailor, Graeme Woodworth)
Standard protocols following the removal of brain tumors include chemotherapy directly applied to the surgical site to kill any cancer cells left behind. This method, however, is only partially effective because it is hard to administer a dose of chemotherapy high enough to sufficiently penetrate the tissue to be effective and low enough to be safe for the patient and healthy tissue. Furthermore, previous versions of drug-loaded nanoparticles typically adhere to the surgical site and do not penetrate into the tissue.
These newly engineered nanoparticles overcome this challenge. Elizabeth Nance, a graduate student in chemical and biomolecular engineering, and Johns Hopkins neurosurgeon Graeme Woodworth, suspected that drug penetration might be improved if drug-delivery nanoparticles interacted minimally with their surroundings. Nance achieved this by coating nano-scale beads with a dense layer of PEG or poly(ethylene glycol). The team then injected the coated beads, which had been marked with a fluorescent tag, into slices of rodent and human brain tissue. 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 results were similar when biodegradable nanoparticles carrying the chemotherapy drug paclitaxel and coated with PEG were used. “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,” said 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, like multiple sclerosis, stroke, traumatic brain injury, Alzheimer’s and Parkinson’s.” Another goal for the team is to be able to administer their nanoparticles intravenously, which is research they have already begun.
Additional authors on the paper include Kurt Sailor, Ting-Yu Shih, Qingguo Xu, Ganesh Swaminathan, Dennis Xiang, and Charles Eberhart, all from The Johns Hopkins University.