Published by the Students of Johns Hopkins since 1896
October 16, 2021

Nanoparticle study improves drug delivery to the brain

By ERICK SUN | September 20, 2012

In recent years, the technology of nanoparticles has become a fascinating area of research for scientists. Nanoparticles are defined as anything 100 nanometers or less, and they have incredible potential for medical uses due to their small size and unique properties.

As objects become smaller and smaller towards the nanoparticle size, they often become more reactive with the compounds around them. Among other uses, researchers have begun utilizing this property by finding ways to pack nanoparticles with drugs. Scientists hope that this will improve drug delivery efficiency and specificity to treat diseases.

Because so many diseases require very specific treatment, the ability to enhance drug delivery offers a major upgrade in patient treatment, which could have major medical and financial implications.

At the Hopkins School of Medicine, a team of researchers led by Elizabeth Nance of the Wilmer Eye Institute recently published an article in Science looking at improving mechanisms of nanoparticle diffusion through brain tissue. Previous studies had shown that only substances 64 nanometer or smaller in diameter could move through the brain extracellular space (ECS) at a reasonable rate.

Such a small space proved difficult for researchers working with nanoparticles typically in the 100 nanometer size, which were unable to move through the ECS well enough to deliver their contents.

The prevailing theory had been that the nanoparticles interacted with the brain tissue, becoming stuck early on and thus preventing the nanoparticles from traveling deep into the tissue to deliver the drug.

To counteract this problem, the team at Hopkins coated their nanoparticles with a layer of poly(ethylene glycol) (PEG) in an attempt to reduce nanoparticle-tissue interactions, thereby freeing the nanoparticles to travel through the tissue unopposed.

What they found was incredibly promising: compared to the previous diffusion size limit of 64 nanometer, particles up to 114 nanometer in diameter were able to move through the ECS with good mobility. Although it seems counterintuitive that increasing the size of a particle with a coating increases diffusion rates, the key that led Nance and others to their hypothesis was the fact that it was not size hindering nanoparticle movement, so much as the molecular interactions creating adhesion between the nanoparticles and the brain tissue.

Therefore, by coating the nanoparticle and eliminating these interactions, the nanoparticles were able to make full use of the brain tissue’s pores and travel efficiently through the ECS.

The team’s findings, tested in human and rat brain tissue, led them to believe that the brain’s ECS actually contains far more pores that are larger than 100 nanometers in diameter than previously expected. Based on previous data, most estimates of ECS mesh size had been capped at 64 nanometers, and previous experiments had shown that even nanoparticles as small as 40 nanometers in diameter had very limited mobility in brain tissue.

However, by allowing the PEG-coated nanoparticles to make their way through the ECS, unhindered by other intermolecular forces, the group at Hopkins was able to shed new light on the topic.

The new discovery offers an exciting opening to the field of drug delivery to the brain. Previously, drugs that travel through the bloodstream have had a difficult time reaching the brain due to the blood-brain barrier. As a result, research towards drug delivery directly to the brain has been a major area of study for scientists. With this latest development, researchers now have clearer picture of the structure of the brain tissue, which will allow them to develop better methods for brain disease treatment.

Although the step is a small one at the moment, the discovery will certainly be a stepping stone for future advancements in the field of nanoparticles and drug delivery. The Hopkins group believes their work could initially be used for treatment of malignant brain tumors. However, they hope that PEG-coated nanoparticles can eventually become a staple in treating all sorts of central nervous system diseases requiring efficient, localized drug delivery.

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