Excretion of a radiolabelled anticancer biodegradable polymeric implant from the rabbit brain

• Published in: Biomaterials 1995-09, Vol.16 (14), p.1069-1072
• Main Authors: Domb, A.J., Rock, M., Perkin, C., Yipchuck, G., Broxup, B., Villemure, J.G.
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - pharmacokinetics; Antineoplastic Agents, Alkylating - urine; Biodegradation; Biological and medical sciences; Brain - metabolism; brain implant; Carbon Radioisotopes; Carmustine - administration & dosage; Carmustine - pharmacokinetics; Carmustine - urine; Decanoic Acids - chemistry; Decanoic Acids - pharmacokinetics; Decanoic Acids - urine; Dicarboxylic Acids; Drug Implants; Hydroxybenzoate Ethers; Hydroxybenzoates - pharmacokinetics; Hydroxybenzoates - urine; Medical sciences; polyanhydride; Polyesters - chemistry; Rabbits; radioactive polymer; Radiotherapy. Instrumental treatment. Physiotherapy. Reeducation. Rehabilitation, orthophony, crenotherapy. Diet therapy and various other treatments (general aspects); Technology. Biomaterials. Equipments. Material. Instrumentation
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/0142-9612(95)98902-Q

The elimination of a clinically used anticancer biodegradable polymer implant (Gliadel ™) 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 14C-SA-labelled polymer, another in a 14C-CPP-labelled polymer and two groups with 14C-BCNU in a non-labelled polymer, one for BCNU disposition study and one for residual drug study. In the rabbits implanted with the 14C-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 7d after implantation. In contrast, only 4% of the radioactivity of the 14C-CPP-labelled polymer was found in urine and faeces during this period. However, a drastic increase in the CPP excretion was found after 9d, and at 21 d, 64% of the implanted 14C-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 3d, 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.