This paper reports the development of three-dimensional simulations to study the effect of various factors on the delivery of 1-3-bis(2-chloroethyl)-1-nitrosourea (
BCNU) to
brain tumors. The study yields information on the efficacy of various delivery methods, and the optimal location of
polymer implantation. Two types of
drug deliveries, namely, systemic administration and controlled release from
polymers, were simulated using fluid dynamics analysis package (FIDAP) to predict the temporal and spatial variation of
drug distribution.
Polymer-based delivery provides higher mean concentration, longer
BCNU exposure time and reduced systemic toxicity than bolus injection.
Polymer implanted in the core gives higher concentration of
drug in both the core and viable zone than the
polymer in the viable zone case. The penetration depth of
BCNU is very short. This is because
BCNU can get drained out of the system before diffusing to any appreciable distance. Since transvascular permeation is the dominant means of
BCNU delivery, the interstitial convection has minor effect because of the extremely small transvascular Peclet number. The reaction of
BCNU with brain tissues reduces the
drug concentration in all regions and its effect increases with rate constant. The implantation of
BCNU/
ethylene-vinyl acetate copolymer (EVAc) matrix at the lumen of the viable zone immediately following the surgical removal of 80% of the
tumor may be an effective treatment for the
chemotherapy of
brain tumors. The present study provides a quantitative examination on the working principle of
Gliadel wafer for the treatment of
brain tumors.