Improved Nanoparticles Deliver Drugs into Brain
Diseases of the brain are notoriously challenging to treat, in large part because of the difficulty in getting therapeutic agents across the blood-brain barrier. Researchers from the Johns Hopkins Center of Cancer Nanotechnology Excellence (Hopkins CCNE) report they are one step closer to a drug-delivery system flexible enough to overcome some key challenges posed by brain cancer and other maladies affecting the brain.
In a report published in the journal Science Translational Medicine, the Johns Hopkins team says it has 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,” says Justin Hanes, a project leader at the Hopkins CCNE and director of the Johns Hopkins Center for Nanomedicine.
After surgery to remove a brain tumor, standard treatment protocols include the administering chemotherapy directly to the surgical site to kill any cells left behind that could not be surgically removed. To date, 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 to be effective and low enough to be safe for the patient and healthy tissue.
To overcome this dosage challenge, Dr. Hanes and his colleagues designed nanoparticles that are able to travel faster and further into the brain tissue. While conventional drug-delivery nanoparticles typically stick to cells at the application site and tend to not migrate deeper into the brain, these new nanoparticles, coated with a dense layer of poly(ethylene glycol (PEG) interact minimally with the surrounding tissue and are more able to move out from the injection site.
To test the performance of their slippery nanoparticles, Dr. Hanes and his colleagues 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.
This work, which is detailed in a paper titled, “A dense poly(ethylene glycol) coating improves penetration of large polymeric nanoparticles within brain tissue,” was supported in part by the NCI Alliance for Nanotechnology in Cancer, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.View abstract