Wb. Dang et al., EFFECTS OF GLIADEL(R) WAFER INITIAL MOLECULAR-WEIGHT ON THE EROSION OF WAFER AND RELEASE OF BCNU, Journal of controlled release, 42(1), 1996, pp. 83-92
The GLIADEL(R) wafer is a polyanhydride implant used in the treatment
of malignant glioma, in which the anticancer agent carmustine (BCNU) i
s incorporated into a copolymer matrix consisting of 1,3-bis(p-carboxy
phenoxy)propane (CPP) and sebacic acid (SA) in a 20 to 80 molar ratio
(p(CPP:SA, 20:80)). It is crucial to determine the relationship betwee
n the wafer's initial molecular weight and the erosion rate of polymer
matrix and the subsequent release rate of drug substance BCNU. This s
tudy focuses on the effect of the initial molecular weight of GLIADEL(
R) on polymer erosion and BCNU release from the polymer matrix. Wafer
erosion in vitro was characterized by weight loss, molecular weight ch
ange and the appearance of water soluble CPP and SA in the incubation
medium at 37 degrees C. Wafer erosion and BCNU release were also inves
tigated in the brains of normal rats. It was found that both the in vi
tro and in vivo erosion of wafer is independent of its initial molecul
ar weight, which in this study ranged from 20000-110000 Da. The averag
e molecular weight of the wafer was reduced to less than 10000 Da afte
r 10 h of incubation in phosphate buffered saline (37 degrees C, pH 7.
4) or after implantation in the brains of normal rats, despite the dif
ferences in initial wafer molecular weight. Furthermore, the release o
f carmustine (BCNU) from GLIADEL(R) is a combination of the diffusion
of drug substance and the erosion of polymer matrix. The release rate
of BCNU is also independent of initial wafer molecular weight.