Getting medication to the brain can be tricky because of the blood brain barrier, which acts like a semipermeable wall between the circulatory system and the fluid surrounding the brain to restrict access to the all-important organ. Certain peptides in animal venoms are known to bridge that gap in order to attack the brain and new research hopes to hijack that invasive quality to deliver drugs across the barrier instead.
We've seen other promising methods of getting through the barrier that involve magnetic nanoparticles and the more natural approach of using bubbles, but a team of scientists from the Institute for Research in Biomedicine (IRB) in Barcelona used apamin, a peptide found in the venom of bees that is known to accumulate in the central nervous system of people who have been stung.
"We thought that because the venoms of some animals are able to attack the central nervous system, they should be able to go through the blood-brain barrier and possibly shuttle drugs across it," said IRB's Ernest Giralt, Ph.D.
Of course, Giralt's method of using a toxin to smuggle medication to the brain is a little problematic because of that little issue of toxicity. Giralt explains that the team set out to modify apamin to make it less toxic but still able to cross over the blood brain barrier. This was done by removing the chemicals in apamin that allow it to attach to a potassium channel in neurons.
"This modification made apamin much less toxic, and its ability to cross the blood brain barrier was intact," Giralt says.
Next, the researchers experimented with making their modified medicine courier smaller and invisible to the immune system. The result was a version called Mini-Ap4 that was even better at accessing the brain than the original peptide.
The researchers concede that other similar drug delivery methods are in the works that can also cross the barrier, but they believe the advantage of their technique lies in the fact that Mini-Ap4 has a ring structure rather than the linear peptides used in other approaches. The ring shape makes the modified peptide more resistant to proteases, which are enzymes that break down peptide bonds.
Now that the researchers are confident their modified peptide can travel where it needs to go, the next steps will involve seeing how well it does at actually carrying cargo and delivering medication. The plan is to investigate this using human cells and in mice.
They'll also be doing additional research to ensure that a person allergic to bees wouldn't have a similar reaction to Mini-Ap4.
The researchers presented their work Sunday at the national meeting of the American Chemical Society.
Source: American Chemical Society
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