NANOTECHNOLOGY AND THE BLOOD-BRAIN BARRIER

Your body’s a party and everybody’s invited. Sure, your skin’s a semicompetent bouncer, but once riffraff reaches the dance floor, they have the run of the place, diffusing across the porous walls of the vascular system and through the gaps between your body’s relatively loose matrix of cells. So your body’s evolved ways to deal with riffraff run amok, including straining them through the kidneys or liver, eliminating them via white-blood-cell hit men, and employing a continuous crew of contractors to repair any damage. If the riffraff overwhelm these safeguards, it’s fairly easy for doctors to call in a cavalry of antibiotics or a good dose of activated charcoal.

Your brain, however, is a much more exclusive party, with a much better bouncer. Actually, the blood-brain barrier is made up of many bouncers (fatty endothelial cells) standing shoulder to shoulder (tight junctions). These corpulent bouncers stand so tightly together that even VIPs like oxygen can’t squeeze around them, and must enter the party by virtue of being fat-soluble—they dissolve through the bouncers’ fat, entering one side and exiting the other. (Don’t worry: alcohol is fat-soluble too—the party can go on.) Any needed water-soluble substances like glucose and amino acids have to enter through doors made especially for them and them alone—these molecules pass through specialized channels, which act as miniature portals in the barrier.

With the very serious system of the blood-brain barrier in place, nothing unwanted gets in. Ever. And so the brain forgoes many of the body’s safeguards, namely white blood cells, filtering, and much of the subcontractors that repair damage.

Of course, “never” is an overstatement. And this lack of other safeguards means that if even a little bit of riffraff crosses the blood-brain barrier, it can be very, very bad. Not only does the brain itself have few safeguards against infection, but the antibiotic cavalry can’t get in the door to save the day. Also excluded by the blood-brain barrier are cancer drugs and drugs that target the HIV virus, which has evolved (as it is wont to do at a frightening pace) to gather and hide in the brain like plotting desperados in a west Texas cave.

Doctors have pioneered a couple interventions to force drugs into the sack of the brain, including increasing osmotic pressure inside the skull, blasting the blood-brain barrier with ultrasound, and surgically implanting a time-release drug-delivery device inside the barrier. As you can imagine, none of these is much fun.

The Blood-Brain Barrier

Enter nanotechnology.

In 2007, researchers at the University of Modena in Italy attached nanobubbles of biodegradable plastic to molecules that naturally pass through the blood-brain barrier and watched as the molecule/plastic pairs were recognized, vetted, and transported into the brain. Researchers hope this transport system will prove an effective method of smuggling drugs past the bouncers. Imagine many thousands of these molecule/plastic pairs and inside each biodegradable plastic bubble an antiretroviral molecule targeting HIV—no more hiding in the brain, pardners.

All the most acute, most powerful, and most deadly diseases, and those which are most difficult to be understood by the inexperienced, fall upon the brain.

—Hippocrates, circa 400 B.C.