Jan. 14, 2002 -- A major stumbling block to treating brain disorders is the blood-brain barrier. This safety net that shields our brain from foreign substances also prevents needed medications from getting to damaged cells. But scientists may have found a way around the problem. When ascorbic acid -- better known as vitamin C -- is chemically attached to certain drugs, it allows them to penetrate the barrier, reaching more of its target cells within the brain.
"We've opened a door for a promising new way to improve delivery of drugs into the brain using a natural nutrient, ascorbic acid," says study leader Stefano Manfredini, professor of pharmaceutical chemistry at the University of Ferrara, Italy.
The findings appear in the Jan. 31 issue of the Journal of Medicinal Chemistry.
Manfredini's team has tested the drug-delivery system only on animals and on human tissue samples but not on living human beings, so much more investigation is needed. But so far, he says, the results are "exciting."
Their work was based on the recent discovery of a receptor, called the SVCT2 transporter, which seems to play a role in the transportation of vitamin C into the brain, where concentrations of the nutrient are normally high. If they attached vitamin C to a drug, they reasoned, the transporter would help the modified drug cross the barrier.
First, they tested the theory in the laboratory with three drugs for brain disorders -- including epilepsy and Alzheimer's -- using tissue samples with the same amount of SVCT2 transporters as in the human blood-brain barrier. In all three cases, the vitamin C significantly increased the amount of drug that interacted with the transporters. This, say the researchers, suggested that more drug would cross the blood-brain barrier in a living organism.
Then they tested one of the modified drugs in mice with induced convulsions. They injected some of the animals with the normal version of the drug and others with the modified version. Only animals that received the drug with attached vitamin C had delayed convulsions -- indicating that the drug was more effective. None of the mice had serious side effects or died from the treatment.
In the report, the researchers add that the findings open new, interesting perspectives for the possibility of obtaining modified drugs effective at crossing the blood-brain barrier. "Further studies are currently ongoing in order to assess and extend this possibility," they write.