PZ opens door to drugs
A professor of pharmaceutical sciences at the School of Pharmacy has received a patent for a new invention that could improve the way drugs are transported to the bloodstream.
Vincent Lee, the Gavin S. Herbert Chair of Pharmaceutical Sciences, said that the new invention is like a “tour guide” that shows drug molecules the best way to reach their destination.
The invention-a small synthetic molecule called PZ-peptide-does its job by opening tight junctions, small spaces that form tunnel-like channels between adjacent cells. Tight junctions are like closed doors, normally allowing only small ions to pass from one side of a cell-layer to the other.
But when PZ-peptide approaches tight junctions between cells that line the intestine, it temporarily increases the size of the junction and allows drug molecules to pass through on their way to blood vessels on the other side.
“The PZ-peptide negotiates with the cell to open its door,” said Lee. After the tight junction opens wide enough to allow the passage of drug molecules, it closes up again a short time later.
Small amounts of the peptide can be mixed with a drug preparation so that the two compounds reach the intestine at the same time. Lee hopes that future development will allow PZ-peptide to be directly coupled to some drugs, lending to nearly absolute specificity of the “open-door” system.
Drugs that could be enhanced by the delivery method include small proteins like insulin, some blood pressure medications, and possibly antiviral drugs.
Since drugs delivered with PZ-peptide are able to reach the bloodstream with high levels of efficiency, use of the PZ-peptide system could mean that drugs that were previously not marketable because of poor absorption rates could find their way to commercial use.
Other substances previously used to help drugs get across a single layer of cells have damaged tight junctions beyond repair, causing irreversible damage and unacceptable side-effects. None has received FDA approval.
PZ-peptide works best where drugs need to pass through only one layer of cells, like the layer that separates the inside of the intestine from the bloodstream. Lee hopes to engineer the PZ-peptide system to work in other tissues, such as the lining of the lung or the thin barrier between circulating blood and brain tissue.
Once the PZ-peptide does its job, it finds its way to the liver and finally out of the body. “Because after all,” said Lee, “you don’t want the tour guide to become part of your family.”
The invention is a molecule made of a short peptide chain-a string of about five amino acids-attached to a complex molecular segment that guarantees the compound won’t get broken down before it does its job.
Lee and his colleagues originally designed PZ-peptide to enter cells rather than to go around them, as part of an experimental protocol. When the peptide entered the cells, the researchers hoped, it would be destroyed. But research team found that instead of entering cells and facing certain degradation, the molecule snuck around them by opening tight junctions. “It had the instinct to use the door instead,” said Lee.
The patent was issued to USC for the research of Lee, whose collaborator, Wan-Ching “Jean” Yen, a former USC graduate student now at Ohio State University, is also on the patent.