Chemotherapuetic Treatment Using Controlled Drug Delivery of BCNU via Nanoparticles
Brendel, Matt; Casey, Molly; Gilbert, Rachel; Spinella, Mel
The most common type of brain tumor is the glioma and despite advances in diagnostic imaging and drug delivery, there are no effective cures. This is due to the malignant glioma’s tendency to recur after treatment, with the recurrence being within a 4cm region from the edge at which it was surgically removed. However, local delivery mechanisms have provided a way for drug to reach the malignant tumors directly. One of these mechanisms is the use of the drug BCNU that is inserted into the cavity via dissolvable Gliadel wafers. These wafers have shown the ability to provide high drug concentrations to a localized area, but at a limited penetration distance of 1 to 2 cm. Consequently, our objective is to improve the design of the Gliadel wafer by encapsulating the BCNU in nanoparticles consisting of PSA with the goal that these nanoparticles will diffuse far enough from the wafers that the drug will reach a higher penetration distance. The drug delivery was modeled in COMSOL, using three governing equations: one to model the diffusion of the nanoparticles from the wafer into the tissue, one to model the diffusion of the drug out of the nanoparticles into the tissue, and another to model interstitial fluid flow in the brain. An axisymmetric cylindrical geometry was used to model the entire complex. The concentration of the BCNU out of the nanoparticles was modeled proportionally to the volume of the nanoparticle that was degraded. To accurately model drug delivery, interstitial fluid flow was taken into account due to its ability to cause a significant convective flux for the transport of macromolecules. The simulation was run for 12 days and a distance of 4cm from the removed tumor was reached above the therapeutic value of 5.394 x 10-12 mg/mm3. This was then compared to the method of BCNU delivery directly from the Gliadel wafers which are in the absence of nanoparticles. The results show that upon reaching the threshold value, the wafer containing nanoparticles diffused further into the brain tissue in comparison to the Gliadel wafer merely containing BCNU. Not only this, but the BCNU was also able to maintain at therapeutic levels for over 24 hours at the goal distance of 4cm from the tumor site. The ability of BCNU to reach a distance of 4cm from the tumor site supports the success of our design. This result strongly suggests that this method of drug delivery may treat the malignant glioma more successfully when compared to alternative cancer treatments. Design recommendations to more accurately model this process include adjustments to the geometry, nanoparticle diffusion and degradation, and assumptions made within the cavity region.