Johns Hopkins associate professor Justin Hanes and doctoral candidate Samuel Lai have demonstrated that PEG-coated nanoparticles have potential use as extended drug-delivery devices. Photo courtesy of THE JOHNS HOPKINS UNIVERSITY
Nanoparticles coated with polyethylene glycol (PEG) have the power to push through the body's sticky mucosal barrier, making them suitable for extended and targeted drug delivery.
Research on the nanoparticles evolved as a team from The Johns Hopkins University was looking for a way to get medications past the sticky barrier that protects organs. Although the mucosal layers shield organs from foreign materials and infection, they can also block drugs from treating those same areas. Many medications are introduced into the body via pills or injections, but this can cause side effects or weaken drug doses at the site. The coated nanoparticles could be a more effective way to target areas that need to be treated.
“The novelty is twofold,” says Justin Hanes, PhD, associate professor of chemical and biomolecular engineering at Johns Hopkins. “It had been previously thought that the mucus mesh size was about 10 to 200 nm at most.” Researchers thought synthetic materials like polymers would be too large to be able to move well through the mesh.
However, the researchers showed that large synthetic particles could indeed move through the mucus mesh. They also demonstrated that a 500-nm particle coated with PEG moves through mucus only four times slower than it goes through water.
In their efforts to find a material that could get through the mucus mesh, the researchers observed the work of Richard Cone, a Johns Hopkins professor. His research had found that some viruses could get through the mucosal barrier. As Hanes' team sought out a material that was dense enough to imitate the characteristics of a virus, they opted for PEG, an uncharged, hydrophilic material.
Because PEG has been shown to be adhesive to mucus, the researchers made the molecular weight of the polymer small enough that it wouldn't support adhesion. Then they coated 200-nm particles with PEG. With high-resolution video microscopy and software, they observed that the nanoparticles were able to pass through the mucus barrier.
“We saw that [the particles] were moving through mucus much faster than any synthetic particle had ever moved through,” explains Hanes. Then they used larger nanoparticles and found that they moved even faster.
“The exciting thing about this is that you can use pretty large particles to go through mucus, and they can overcome the barrier if they are properly coated,” says Hanes, adding that the particles enable an efficient encapsulation of drugs. “The most important point is that when you go from a 100-nm particle to a 500-nm particle, the length over which you can release the drug goes up dramatically.” Drugs encapsulated in the nanoparticles could be released over a period of hours, days, or weeks.
Extended drug release introduces the possibility of using the nanoparticles to deliver antibodies for treating sexually transmitted diseases, influenza, and anthrax, for example. The particles would also be able to provide targeted therapy, as opposed to treatments like chemotherapy that are felt throughout the body. For treating lung conditions such as cancer or inflammation, a dry-powder inhaler could introduce the particles into the organ. In pill form, the nanoparticles would be placed in a capsule that's designed to protect them from degradation in the stomach. The capsule would quickly dissolve in the gastrointestinal tract, thereby releasing the nanoparticles.
The polymer particle used in the research paper is a nondegradable latex material that wouldn't be used in humans, says Hanes. However, his lab is working with a patent-pending biodegradable polymer, which is based on a polymer that has already been used in humans and has the potential to release a range of drugs. PEG is one of the components of the new polymer, and preliminary studies suggest that particles made with this biodegradable material can also move through mucus.
The researchers' findings were published in the January 30 edition of the Proceedings of the National Academy of Sciences.