Effect of dose on the biodistribution and pharmacokinetics of PLGA and PLGA-mPEG nanoparticles

The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA and stealth poly(lactide-co-glycolide)-monomethoxypol y(ethyleneglycol) (PLGA-mPEG) nanoparticles was investigated. The precipita tion-solvent diffusion method was used to prepare PLGA and PLGA-mPEG nanopa rticles labeled with I-125-cholesterylaniline. These were administered intr avenously (i.v.) in mice and at predetermined time intervals the animals we re sacrificed and their tissues were excised and assayed for radioactivity. Within the dose range applied in this study, blood clearance and mononucle ar phagocyte system (MPS) uptake of the PLGA nanoparticles depended on dose whereas they were independent of dose in the case of the PLGA-mPEG nanopar ticles. Increasing the dose, decreased the rates of blood clearance and MPS uptake of the PLGA nanoparticles, indicating a certain degree of MPS satur ation at higher doses of PLGA nanoparticles. The dose affected the distribu tion of PLGA nanoparticles between blood and MPS (liver) but it did nut aff ect the nanoparticle levels in the other tissues. Within the range of doses applied here, the PLGA nanoparticles followed non-linear and dose-dependen t pharmacokinetics whereas the PLGA-mPEG nanoparticles followed linear and dose-independent pharmacokinetics. In addition to the prolonged blood resid ence, the dosage-independence of the pharmacokinetics of the PLGA-mPEG nano particles would provide further advantages for their application in control led drug delivery and in drug targeting. (C) 2001 Elsevier Science B.V. All rights reserved.