Nanoparticles May Help Deliver Drugs through Blood-Brain Barrier 

Paul Harary ’19

Figure 1.  Nanoparticles can be attached to drugs and used to guide therapeutic agents through the blood-brain barrier to targets within the brain (Image Source: Wikimedia Commons)

Researchers at the University of Washington in St. Louis recently discovered a new drug-delivery method that promises to reach targets within the brain with greater efficiency and precision.  By using gold nanoparticles as a drug carrier, the team was able to take advantage of more direct routes to the brain, such as the olfactory pathway.

The blood-brain barrier (BBB) protects the human brain from foreign substances, such as bacteria and neurotoxins, by providing an interface between blood circulating in the body and the brain’s extracellular fluid. The BBB is comprised of a series of endothelial cells separated by small openings called tight junctions. Molecules critical to neural function, such as glucose and amino acids, are small enough to pass through the tight junctions between the endothelial cells, while larger, microscopic objects are kept out. In this way, the BBB acts as a filter against substances that may injure the brain and also maintains a stable environment in the brain extracellular fluid.

However, this very same filtration mechanism often poses a problem when trying to reach drug targets within the brain.  Orally administered pills, the traditional drug-delivery method, are often imprecise and unable to reach receptors within the brain, since they must first pass through the BBB. Direct injection, on the other hand, is swifter but significantly more invasive and carries greater risks.

A team of engineers at Washington University in St. Louis proposed a novel approach to the problem that the BBB poses for drug-delivery. Administered via a nanoparticle nasal spray, their medication only had to pass through the olfactory bulb and olfactory cortex to reach its intended target within the brain. The olfactory pathway is the shortest route to the brain and, as a result, aerosol-based drug therapies can be delivered to neural regions in as little as thirty minutes to one hour.

The team, which included Ramesh Raliya of the School of Engineering and Applied Science, postdoctoral fellow Debajit Saha, and Assistant Vice Chancellor Pratim Biswas, engineered an aerosol using gold nanoparticles and applied it to the antennae of invertebrate locusts, which have an olfactory pathway similar to that of humans. After tagging these nanoparticles with fluorescent markers, the scientists visualized the progression of the aerosol from the locusts’ antennae, through the olfactory nerves, and finally through the BBB and into the brain.  Due to the small size of the nanoparticles, this entire process took place in minutes rather than hours.

The researchers had to ensure, however, that the foreign nanoparticles did not disrupt normal brain function. To study this risk, Saha introduced the nasal spray and tracked the electrophysiological responses of the locusts’ olfactory neurons.  Comparing observations from before and after the delivery of the gold nanoparticles, he concluded there was no significant change.

The team’s work holds promise for future research in aerosolized drug delivery. The next steps will involve the fusion of the nanoparticles with the desired medications and the establishment of appropriate dosages.  By demonstrating the viability of an aerosol-based nanoparticle drug delivery method, the team has opened up a host of possibilities for swifter and more precise drug-delivery across the BBB.

References:

  1. Washington University in St. Louis. (2017, April 12). Nanoparticle research tested in locusts focuses on new drug-delivery method.  ScienceDaily . Retrieved April 14, 2017 from sciencedaily.com/releases/2017/04/170412145225.htm
  2. Raliya, R., Saha, D., Chadha, T. S., Raman, B., & Biswas, P. (2017). Non-invasive aerosol delivery and transport of gold nanoparticles to the brain. Scientific Reports, 7, 44718. doi:10.1038/srep44718
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