Distribution, kinetics and elimination of radioactivity after intravenous and intramuscular injection of 14C-savoxepine loaded poly( D, L-lactic acid) nanospheres to rats

• Published in: Journal of controlled release Vol. 29; no. 1; pp. 97 - 104
• Main Authors: Allémann, E., Gurny, R., Doelker, E., Skinner, F.S., Schütz, H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.02.1994; Elsevier
• Subjects: Biodistribution and elimination; Biological and medical sciences; General pharmacology; Intramuscular injection; Intravenous injection; Medical sciences; Nanoparticle; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Poly( D, L-lactic acid); Sustained release; Sustained release; Poly( D, L-lactic acid); Intramuscular injection; Biodistribution and elimination; Intravenous injection; Nanoparticle; Pharmaceutical technology; Intravenous administration; Rat; Biodegradability; Controlled release form; Neuroleptic; Control release polymer; Psychotropic; Rodentia; Intramuscular administration; Vertebrata; Lactic acid polymer; Mammalia; Animal; Dosage form; Pharmacokinetics
• ISSN: 0168-3659; 1873-4995
• DOI: 10.1016/0168-3659(94)90125-2

Biodegradable poly( D, L-lactic acid) nanoparticles loaded with 14C-savoxepine were prepared using a salting-out process avoiding the use of chlorinated solvents and surfactants. Their sustained release properties after intravenous (i.v.) and intramuscular (i.m.) injection were assessed in rats. The pharmacokinetics, excretion and distribution of radioactive substances derived from 14C-savoxepine loaded in particles and as a free test compound in solution were determined by liquid scintillation 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 initial radioactivity remained in the rats, mainly at the injection site. Stable plasma levels of 14C were observed over 7 days. After injection of the free compound in solution (i.v. or i.m.) 50% of the initial dose of radio-activity was eliminated in less than one day. After i.v. injection of the nanoparticles an effective sustained release was observed. However, the poly (vinyl alcohol) coating of these nanoparticles could not prevent a massive uptake by the reticuloendothelial system.