Brain Absorption Assay Advance
Estimating the unbound fraction of a compound in the brain is a key parameter when developing drugs for the central nervous system. Currently, dialysis systems and brain slice assays are the methods of choice. Hinnerk Boriss, Ph.D., CEO of Sovicell, described the company’s two-year-old Transil technology, which, he said, is faster and cheaper than other methods and has been shown to be as accurate as dialysis in work recently published by GlaxoSmithKline.
“The old way of looking at how difficult it is for a drug to pass the blood brain barrier (BBB) is actually the wrong question. Every drug gets into the brain, just to different extents. The right question is what happens when the drug actually gets into brain,” said Dr. Boriss. He noted that many drugs have drastically differing BBB penetration profiles—e.g., Sumatriptan (poor BBB penetrator) and Sertraline (high penetrator)—but are also effective in the brain.
Transil uses porous silica beads as a carrier for biological molecules such as membranes and proteins. Sovicell’s Transil Brain Absorption kit is made with reconstituted porcine brain lipid membranes immobilized on the beads.
After mixing and incubation for two minutes the beads are separated by low-speed centrifugation.
“If you do LC/MS, which is the standard method in this field, then you need longer gradients to interpolate the biological matrix from the compound of interest to quantify them. With our method there is no need to separate the biological matrix because that’s the beads. We just remove the beads and you can straight away analyze and quantify the samples. It’s three to four times faster for analyzing and quantifying the results.”
Dr. Boriss emphasized that lipid binding is a more important indicator than protein binding “because there are very few proteins that contribute to binding. It’s about 28 micromolar albumin that contributes to binding versus about 125 micromolar lipid and the affinity of drugs to lipids is three to four orders of magnitude higher on average—higher than binding to albumin.”
Sovicell offers assay chips and assay services on a small scale. Dr. Boriss believes the technology has the potential to enable companies to ramp up screening activities, reduce investments in instruments, or redirect other activities to instruments previously tied up with processing samples from dialysis.