Traversing the blood-brain barrier is a challenge for drug developers. Now, after testing the method in locusts, a team of engineers shows how an aerosol nasal spray containing gold nanoparticles may offer a non-invasive and rapid way to deliver drugs to the brain.
The team - from the University of Washington in St. Louis (WUSTL), MO - describes the proof-of-concept research in the journal Scientific Reports.
For the brain to function, it must operate in a tightly controlled chemical environment that is protected from the more varied fluctuations of the rest of the body.
This stable environment is maintained by the blood-brain barrier, which comprises layers of specialized cells in the inner linings of the small blood vessels in the brain and spinal cord.
The blood-brain barrier prevents toxins from entering the tissues of the brain and spinal cord. Unfortunately, it does the job so well that it also keeps out many drugs, such as those used to kill cancer cells.
One way to overcome this is to deliver drugs to the brain using injections. However, such invasive approaches are risky in that they can damage tissue and have little control over the distribution of the drugs from the point of injection, note the study researchers.
Thus, in a bid to find an effective and less risky alternative, the WUSTL team decided to explore the potential of using nanoparticles to carry drugs to the brain through the nose.
Nose offers easy access to the brain
Interest in using nanotechnology - the ability to control matter at the atomic and molecular scale - to develop new diagnostic tools and treatments is growing, note the authors in their study report.
A number of new nanomaterials have been used to carry drugs to specific targets in organs and tissues. These appear to maximize drug effectiveness while minimizing side effects.
Co-author Barani Raman, associate professor of biomedical engineering, says that the nose offers the shortest - and most likely the easiest - route to the brain.
He and his colleagues note that from various studies, gold nanoparticles have emerged as the material of choice for drug delivery. They are relatively easy to synthesize and customize, and they have good biocompatibility.
The team developed a new aerosol diffusion method that deposits gold nanoparticles in the upper regions of the nasal cavity. They produced the nanoparticles to a controlled shape, size, and surface charge, and tagged them with fluorescent markers so that they could track them.
Locusts offer a good model of the human blood-brain barrier
Prof. Raman explains that in humans, to reach the brain through the nose, the nanoparticles have to travel through the olfactory bulb and then the olfactory cortex, "two relays and you've reached the cortex," he says.
"The same is true for invertebrate olfactory circuitry," he adds, "although the latter is a relatively simpler system, with [a] supraesophageal ganglion instead of an olfactory bulb and cortex."
The team exposed the locusts' antennae to the aerosol and tracked the progress of the tagged nanoparticles. Within a few minutes, the nanoparticles had traversed the insects' olfactory circuitry, passed through the brain-blood barrier, and suffused the brain tissue.
The team showed that the nanoparticles did not affect the insects' brain function. They measured the electrophysiological responses of the locusts' olfactory neurons before and after treatment and found no discernible difference up to several hours afterwards.
The researchers say that the next stage of their research will be to load the nanoparticles with different drugs and use ultrasound to target precise doses to reach specific areas of the brain. Such methods could potentially make a big difference to the treatment of brain tumors.
"The blood-brain barrier protects the brain from foreign substances in the blood that may injure the brain. But when we need to deliver something there, getting through that barrier is difficult and invasive. Our non-invasive technique can deliver drugs via nanoparticles, so there's less risk and better response times."
Prof. Barani Raman