Metabolic disposition and elimination studies of a radiolabelled biodegradable polymeric implant in the rat brain.
The metabolic disposition and elimination process of the anhydride co-polymer poly[1,3-bis(p-carboxy-phenoxypropane):sebacic acid] 20:80 [P(CPP:Sa)20:80] implanted in the rat brain was studied. Two polymers were prepared, one with [14C]SA and unlabelled CPP, and the other co-polymer with [14C]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 [14C]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 [14C]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.
Domb
A J
AJ
Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel.
Rock
M
M
Schwartz
J
J
Perkin
C
C
Yipchuk
G
G
Broxup
B
B
Villemure
J G
JG
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002330:Carmustine / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D002626:Chemistry, Pharmaceutical; D003652:Decanoic Acids / Q000493:pharmacokinetics*; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D005260:Female; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates / Q000493:pharmacokinetics*; D008297:Male; D019736:Prostheses and Implants; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D003652:Decanoic Acids; D003998:Dicarboxylic Acids; D004337:Drug Carriers; D062425:Hydroxybenzoate Ethers; D062385:Hydroxybenzoates; C078320:1,3-bis(4-carboxyphenoxy)propane; C011107:sebacic acid; D002330:Carmustine