BRAIN PHANTOM PROJECT
Glioblastoma Multiforme (GBM) is a prevalent and aggressive form of primary brain tumor afflicting about 20,000 patients in the US every year. The prognosis for patients diagnosed with GBM is in the order of months and the treatment of this disease, which confers a mere increase of 8 weeks in patients with recurrent tumors and 18 weeks in patients with first time tumors, has shown almost no improvement over the last four decades. The current treatment involves a combination of surgical resection and insertion of BCNU loaded polymer wafers (Gliadel?) followed by chemo or radiotherapy. The Gliadel? wafers are known to stack and dislocate in the surgical cavity due to postsurgical inflammation resulting in suboptimal drug delivery. In addition, the wafers are loaded with only a single drug type and even that at a much lower than tolerable dose. Yet, no efforts to address these deficiencies have been identified. This may be in large part due to the lack of an adequate brain model. As such, we have initiated the design and development of a novel polymer implant device to address the drawbacks of the current wafers and have in the process developed a preliminary brain phantom model using 0.6% agarose gel cast in a life-size plastic mold to test our device. This model has incorporated the diffusion properties of the brain tissue and the simulation of the effects of postsurgical inflammation. We have also developed a preliminary computer simulation model based on an appropriate mathematical model described in the literature which will be used to validate our phantom model as well as provide a basis for a tool that may be used to predict patient outcomes in the clinical setting. The computer simulation has been validated through the generation of results which concur with data from published literature and has also been used to establish that the morphology of the implant device has a significant effect on the drug delivery in the brain. We developed an electrospun polymer (polycaprolactone or PCL) mesh loaded with a drug substitute (fluorescein) and carried out preliminary tests to demonstrate empirically the effect of morphology on drug release and delivery. Empirical determination of the diffusion parameters were incorporated in our phantom and computer model to cross-validate their design and establish proof of concept. The simultaneous development of all three aspects has provided a justification for the preferential development of the implant device in spring or coil morphology as opposed to a mesh or mat morphology and will serve to continually cross-validate our designs as the project proceeds. PCL as the testing polymer has been deemed inappropriate due to limitations on fabrication (extrusion) as well as a very slow degradation rate. Suggestions for the exploration of deployment mechanisms of the spring or coil have also been made.
drug delivery in the brain; Glioblastoma Multiforme; agarose brain phantom; computer simulation