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)–monomethoxypoly(ethyleneglycol) (PLGA–mPEG) nanoparticles was investigated. The precipitation-solvent diffusion method was used to prepare PLGA and PLGA–mPEG nanopa...

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Bibliographic Details
Published in:International journal of pharmaceutics 2001-06, Vol.221 (1), p.143-152
Main Authors: Panagi, Z, Beletsi, A, Evangelatos, Gregory, Livaniou, E, Ithakissios, D.S, Avgoustakis, K
Format: Article
Language:English
Subjects:
Animals
Area Under Curve
Biocompatible Materials
Biodistribution
Biological and medical sciences
Dose-Response Relationship, Drug
Effect of dose
Female
General pharmacology
Half-Life
Injections, Intravenous
Lactic Acid - administration & dosage
Lactic Acid - pharmacokinetics
Medical sciences
Metabolic Clearance Rate
Mice
Particle Size
Pharmaceutical technology. Pharmaceutical industry
Pharmacokinetics
Pharmacology. Drug treatments
poly(Lactide-co-glycolide)
poly(Lactide-co-glycolide)-monomethoxy(polyethyleneglycol)
Polyethylene Glycols - administration & dosage
Polyethylene Glycols - pharmacokinetics
Polyglactin 910 - administration & dosage
Polyglactin 910 - pharmacokinetics
Polyglycolic Acid - administration & dosage
Polyglycolic Acid - pharmacokinetics
Polylactic Acid-Polyglycolic Acid Copolymer
Polymers - administration & dosage
Polymers - pharmacokinetics
Tissue Distribution
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Summary:The effect of nanoparticle dose on the biodistribution and pharmacokinetics of conventional PLGA and stealth poly(Lactide-co-glycolide)–monomethoxypoly(ethyleneglycol) (PLGA–mPEG) nanoparticles was investigated. The precipitation-solvent diffusion method was used to prepare PLGA and PLGA–mPEG nanoparticles labeled with 125I-cholesterylaniline. These were administered intravenously (i.v.) in mice and at predetermined time intervals the animals were sacrificed and their tissues were excised and assayed for radioactivity. Within the dose range applied in this study, blood clearance and mononuclear phagocyte system (MPS) uptake of the PLGA nanoparticles depended on dose whereas they were independent of dose in the case of the PLGA–mPEG nanoparticles. Increasing the dose, decreased the rates of blood clearance and MPS uptake of the PLGA nanoparticles, indicating a certain degree of MPS saturation at higher doses of PLGA nanoparticles. The dose affected the distribution of PLGA nanoparticles between blood and MPS (liver) but it did not affect the nanoparticle levels in the other tissues. Within the range of doses applied here, the PLGA nanoparticles followed non-linear and dose-dependent pharmacokinetics whereas the PLGA–mPEG nanoparticles followed linear and dose-independent pharmacokinetics. In addition to the prolonged blood residence, the dosage-independence of the pharmacokinetics of the PLGA–mPEG nanoparticles would provide further advantages for their application in controlled drug delivery and in drug targeting.
ISSN:0378-5173
1873-3476
DOI:10.1016/S0378-5173(01)00676-7