Researchers at the University of Michigan in Ann Arbor have found a way to make insoluble drugs dissolve using unstable metal organic frameworks.
A 2012 study found that 90 percent of drugs in development don’t dissolve well or at all in the body. Metal organic frameworks are rigid, porous structures composed of metal linked by organic ligands. The drugs are packed into the pores of these frameworks, where they were kept from crystalizing. Instead, they remained in an amorphous form. Crystalized drugs are less soluble and therefore less bioavailable – less of the drug crosses into the bloodstream.
“It struck us that while everyone was shooting for stable MOFs, we could use what we had learned about instability of MOFs to get a degradable substance that would rapidly release drugs. It was a really unexpected finding,” says Adam Matzger, the Charles G. Overberger collegiate professor of chemistry and a professor of macromolecular science and engineering.
Previously, polymers were used to hold drug compounds in an amorphous state. The molecules, however, still could migrate and crystalize in the polymer, affecting solubility and how much of the drug was bioavailable. Because metal organic frameworks hold drug molecules apart but quickly decompose, drug dosage is easily controlled. The drug compounds cross into the bloodstream and the metal organic framework dissolves in the body.
The researchers used MOF-5, a type of metal organic framework, for a few reasons. First, its metal component is zinc, which has low toxicity and is used in many supplements. Its organic component is an acid called terephthalic acid. The researchers found that it is also relatively unstable.
“What we do here is we increase the solubility while guaranteeing dosage stability,” says Matzger. “This approach is relatively universal. We show it for three drugs, but the fact that the pores are too small to allow a crystal to form is going to be true for all drugs.”
The study is published in the journal Angewandte Chemie.