Design of Polymer-Grafted Drugs

 

David Trombly

dmt564@che.utexas.edu

Office: CPE 3.402

Phone: 512-471-6754

 

A common issue facing drug designers is the fact that proteins in the blood quickly adsorb by Van Der Waals forces to drugs in the blood, which can lead to either thrombosis (clogging of blood vessels) or uptake by the immune system.  To prevent this, drug designers graft polymer chains to the surface of the drug in order to introduce repulsion between the drug and blood proteins.  By approximating the drug and the protein as spheres and using self-consistent field theory (SCFT) to describe the chains grafted to the drug, we are able to model the system.  In doing so, we obtain results that can be used to help experimentalist design better polymer-grafted drugs as a function of design parameters such as grafting density, sphere size, and the length of the grafted chains.

Using our model we are able to view polymer density profiles such as the one above.  Our most crucial results are energies of interaction between the protein and the polymer grafted drug.  By scaling these energies, we are able to map them approximately onto one curve.  This curve (shown below) can then be used to predict the energy of interaction between a protein and a polymer grafted drug within the range of parameters we studies. 

For more about this topic, see Trombly, D and Ganesan, V Journal of Polymer Science, Part B Volume: 47, Issue: 24, Pages: 2566-2577