EXCRETION OF A RADIOLABELED ANTICANCER BIODEGRADABLE POLYMERIC IMPLANT FROM THE RABBIT BRAIN

The elimination of a clinically used anticancer biodegradable polymer implant (GliadelTM) in the rabbit brain was studied. The implant is composed of N,N-bis(2-chloroethyl)-N-nitrosourea (BCNU) (1.6 wt%) dispersed in a copolyanhydride matrix of 1,3-bis(p-carboxyphenoxypropane) (CPP) and sebacic acid (SA) in a 20:80 molar ratio. Four groups of rabbits were implanted with wafers loaded with BCNU, one in a C-14-SA-labelled polymer, another in a C-14-CPP-labelled polymer and two groups with C-14-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the C-14-SA-labelled polymer, approximately 10% of the radioactivity was found in the urine and 2% in the faeces, and about 10% remained in the device 7 d after implantation. In contrast, only 4% of the radioactivity of the C-14-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9 d, and at 21 d, 64% of the implanted C-14-CPP was found in the urine and faeces, and 29% was still in the recovered wafers. Approximately 50% of the BCNU in the wafers was released in 3 d, and over 95% was released after 6 d in the rabbit brain. This study demonstrates that BCNU-loaded polyanhydride is biodegradable and is excreted from the body primarily through the renal system. The water-soluble components SA and BCNU were rapidly excreted, while the insoluble CPP was gradually eliminated after a lag time of 9 d.