METABOLIC DISPOSITION AND ELIMINATION STUDIES OF A RADIOLABELED BIODEGRADABLE POLYMERIC IMPLANT IN THE RAT-BRAIN

The metabolic disposition and elimination process of the anhydride co-polymer poly[1,3-bis(p-carboxyphenoxypropane):sebacic acid] 20:80 [P(CPP:SA)20:80] implanted in the rat brain was studied. Two polymers were prepared, one with [C-14]SA and unlabelled CPP, and the other co-polymer with [C-14]CPP and unlabelled SA. With these two polymers we were able to study the metabolic disposition of each monomer after polymer degradation. Polymer wafers loaded with N,N-bis(2-chloroethyl)-N-nitrosourea or without the drug were implanted in the rat brain. For the rats implanted with the [C-14]SA-labelled polymer, approximately 40% of the radioactivity was found in the expired CO2, 10% in the urine, about 2% in the faeces and about 10% remained in the device 7 d after implantation. On the other hand, only 4% of the [C-14]CPP monomer was eliminated by urine and faeces during this period. The drug-loaded polymer degraded faster than the blank polymer. This study supports the theory that the polymer is a biodegradable material that can be used for the direct and specific delivery of drugs into a targeted organ and can provide continued release of drugs over a period of time.