"We started with a model I'd previously developed, then added in some features that allow us to model degradation of the delivery system by enzymes," Sakiyama-Elbert said. "Specifically, we added a component where we can model what would happen if there is a cell in part of the delivery system and how that would affect release throughout the delivery system.
"Before you only could address what would happen in a culture dish with no cells around it. We're really interested in what will happen in cell culture or an animal model where there will be active cell-mediated degradation. We are trying to get closer to the real situation." The results were published in the January 2005 issue of Acta Biomateriali. The work was supported by a grant from the Whitaker Foundation. Sakiyama-Elbert said lots of researchers are adopting the concept of affinity-based drug delivery systems, and the Washington University library screening technique and mathematical model together provide a good tool to expand the usefulness of these approaches.
'"One interesting thing we've found in this work is that it appears the activities of the drugs that we're delivering vary with the affinity of the binding site," she said. "We're not sure if that's a function of the affinity controlling the rate of release or if there is actually some separate biological modulator that's being affected.
"The good thing, though, is that we've identified several different affinities of binding sites so we can now test whether it's the affinity or the rate of release and determine what's really going on."
This ability is important for researchers to get insight into the biological activity of different drugs and how they might be modulated for drug release.
"We have low, medium and high affinity binding proteins," Sakiyama-Elbert. "We can look at fast and
Contact: Tony Fitzpatrick
Washington University in St. Louis