Research Description:

Models for Macromolecular Drug Delivery in White Matter

In the improvement of drug delivery to the brain and spinal cord, an important area of research is the development of experimental nervous tissue transport models. Such in-vitro models are useful for studying the convection and diffusion patterns of macromolecular drugs following direct tissue infusion.

To improve these microinfusion techniques, we need to have an in-vitro model with which to test outside the body. The transport in white matter depends upon axonal fiber alignment and requires a physical model that mimics its properties. In order to study white matter, we need to mimic the anisotropy. We are looking at Trevigel, a transparent polymer gel, as our model since it is porous and water-soluble and can mimic the interstitial space of nervous tissue.

To test this transport model, we will couple a macro tracer with dye and inject this into the model. Formulation parameters will be varied until quantitative distribution measures mimic the distribution of similar tracers in white matter. Since white matter contains aligned axonal fibers that produce an elliptical distribution pattern, we will introduce polymer fibers into the gel and force fiber alignment. One method of doing so involves stirring the fibers into the gel in a beaker and then allowing it to solidify. Another proposed method involves creating molds with fixed polymer fibers that span the mold interior. With such a mold, the gel could be replaced later by another gel for further testing. With these methods, we will work to develop a functional experimental nervous tissue model.

The end objective of the research is to quantify drug delivery and infusion into white matter, which will aid targeted treatment of many neurodegenerative diseases.