Drug Delivery via GLIADEL Wafer for Treatment of Glioblastoma Multiforme (GBM)
Ericksen, William Leif; Fortin, Lyndsey; Hou, Cheryl; Shum, Katrina
Glioblastoma multiforme (GBM), one of the most common primary glial tumors, is often treated with tumor resection surgery combined with GLIADEL wafers containing carmustine. These wafers are made with a degradable polymer that releases carmustine over a period of 5 days. Due to the localized nature of the release, no pharmacokinetic measurements have been taken in humans. In order to study the mass transfer of carmustine, COMSOL Multiphysics was used model the process and solve the transient convection-diffusion problem involved. A 2D axisymmetric geometry was used as a simplified schematic involving the wafer, tumor tissue, and normal tissue regions. Input parameters of diffusivity, reaction rates, and velocities were obtained from research involving carmustine drug delivery in human and monkey tissues. Results obtained showed a large initial increase of drug concentration within the first 12 hours localized within the tumor, followed by an exponential decrease during the remaining time period. This shows that the majority of cellular death was within the tumor. Results also indicated that elimination rate, velocity, and diffusivity were sensitive parameters. Furthermore, the model gave insight into what parameters can be changed in order to increase the concentration of carmustine in the tumor and decrease the concentration in the healthy tissue. Carmustine must be delivered to the tumor tissue at a certain concentration to be effective, so optimizing the parameters involved would create a better drug delivery system.
Drug delivery; Glioblastoma Multiforme; carmustine