BOSTON--Treating diseases of the brain, such as cancers, meningitis and infections, has been a formidable task for drug discovery and development because of the challenge of getting drugs across the blood-brain barrier (BBB).
Investigators from the University of California, Davis, have designed silicon nanoparticles that could be capable of penetrating this protective barrier. The scientists presented their findings during a symposium at the American Society for Microbiology annual meeting on May 17.
The team observed that the fungal pathogen Cryptococcus neoformans, a yeast capable of causing fungal meningitis in immunocompromised individuals, is able to cross the BBB.
When they knocked out a certain enzyme, called a metalloprotease (Mpr1), the researchers found that C. neoformans lost much of its ability to cross the BBB in a mouse model.
When this metalloprotease is expressed in baker's yeast, Saccharomyces cerevisiae, the yeast gains the ability to cross the BBB in an in vitro model. This finding shows that Mpr1 may not require much else to promote crossing the BBB, suggesting a possible use in the development of a novel drug-delivery system.
Using this idea, the investigators have produced silicon nanoparticles and combined them with Mpr1 to form nanocarriers. Silicon nanoparticles are relatively nontoxic, easy to chemically manipulate, and traceable in the body, making them a good candidate for use in a delivery platform.
"We intend to load these nanoparticles up with antineoplastic drugs and test them in a model of brain cancer," said University of California, Davis, researcher John Uhrig during a symposium presentation of his findings.
Current treatment methods for brain disorders are not ideal, since most require either larger doses of the drug, which can have harsh side effects, or injecting the drug through the barrier, which compromises its integrity. A drug delivery system that gets drugs across the BBB would enable more efficient treatment for brain diseases and could potentially lessen side effects from high doses of directly injected drugs.
- see the study abstract