Just add water
Chemists from the University of Michigan offer a solution for insoluble drugs
Stable metal organic frameworks are valued for their ability to capture carbon dioxide or collect atmospheric water, but University of Michigan researchers have figured out how to use unstable organometallic frameworks as a drug delivery system, writes a press release Just add water: U-M chemists suggest a fix for insoluble drugs.
According to a study conducted in 2012, ninety percent of the drugs being developed are poorly or do not dissolve in the body at all. Organometallic frameworks, or IOCs, are rigid porous structures consisting of metal connected by organic ligands. While researching unstable IOCs, University of Michigan chemist Adam Matzger realized that they could work as a delivery system for these types of drugs.
"It struck us that while everyone was fighting for stable IOCs, we could use what we learned about the instability of the IOC to get a decomposable substance that quickly releases drugs. It was a really unexpected discovery," said Matzger, professor of chemistry and macromolecular science and technology.
According to Matzger, the IOC delivery system uses a single strategy for delivering insoluble drugs. The strategy is to deliver them in an amorphous form, which means that the drugs will not crystallize. Once the drug compounds crystallize, they become less soluble and therefore less bioavailable, which means that less of the drug enters the bloodstream.
IOCs can keep these drugs in an amorphous state due to their porous structure. The IOC-5, in particular, looks like a set of cubes stacked on top of each other: an image of an infinitely repeating three-dimensional grid. When researchers load a drug into this mesh, the pores in the IOC separate the drug molecules, keeping the compound in the desired amorphous state.
Researchers have previously used polymers to keep drug compounds in an amorphous state, but drug molecules can still migrate and crystallize in the polymer, which affects solubility and, consequently, how much of the drug is bioavailable. According to Matzger, since the IOC rigidly separates the drug molecules, but decomposes quickly, the dosage of the drug is easy to control. The compound itself passes into the bloodstream, while the IOC decomposes in the body.
The researchers decided to use the IOC-5 for several reasons. Firstly, its metallic component is zinc, a low–toxicity metal used in many additives, and the organic component is an acid called terephthalic acid. Secondly, the IOC-5 is relatively unstable, which the researchers demonstrated in a separate paper that studied the stability of various IOCs.
"What we're doing is increasing solubility by ensuring dosage stability," Matzger said. "This approach is relatively universal. We have demonstrated its effectiveness for three drugs, but the fact that the pores are too small to allow the crystal to form will be true for all drugs."
Portal "Eternal youth" http://vechnayamolodost.ru