DISTRIBUTION, KINETICS AND ELIMINATION OF RADIOACTIVITY AFTER INTRAVENOUS AND INTRAMUSCULAR INJECTION OF C-14 SAVOXEPINE LOADED POLY(D,L-LACTIC ACID) NANOSPHERES TO RATS

Biodegradable poly(D,L-lactic acid) nanoparticles loaded with C-14-sav oxepine were prepared using a salting-out process avoiding the use of chlorinated solvents and surfactants. Their sustained release properti es after intravenous (i.v.) and intramuscular (i.m.) injection were as sessed in rats. The pharmacokinetics, excretion and distribution of ra dioactive substances derived from C-14-savoxepine loaded in particles and as a free test compound in solution were determined by liquid scin tillation counting. Particles with a mean diameter of 736 nm and 8.4% compound loading exhibited a sustained release over more than one week . 5.4 days after i.m. injection of the nanoparticles 50% of the initia l radioactivity remained in the rats, mainly at the injection site. St able plasma levels of C-14 Were observed over 7 days. After injection of the free compound in solution (i.v. or i.m.) 50% of the initial dos e of radioactivity was eliminated in less than one day. After i.v. inj ection of the nanoparticles an effective sustained release was observe d. However, the poly (vinyl alcohol) coating of these nanoparticles co uld not prevent a massive uptake by the reticuloendothelial system.