Poly(diethyl methylidenemalonate) nanoparticles as a potential drug carrier: preparation, distribution and elimination after intravenous and peroral administration to mice.
Polymerization of diethyl methylidenemalonate (DEMM, 1a) in 0.1 M phosphate buffer containing 1% dextran 70 yields nanoparticles of a diameter ranging from 140 to 250 nm depending on the pH value (6.7 to 8.7). The weight-average and number-average molecular weight of the resulting polymer were 3791 and 1084, respectively. Approximately 95% of the 14C-labeled poly(DEMM) nanoparticles were found in liver and spleen 1 h after iv administration. A statistically significant (p less than 0.01) approximately 10% decrease of the radioactivity was observed in the liver over a 3-month period. The poly(DEMM) nanoparticles were not absorbed and were totally cleared from the gastrointestinal tract 24 h after oral dosage. The very slow bioelimination process observed after iv administration limits the usefulness of poly(DEMM) nanoparticles as a systemic drug carrier. Nevertheless, their oral administration as bioavailability enhancers can be envisaged. Moreover, the fact that nanoparticles are readily produced in a medium near neutrality should be emphasized.
De Keyser
J L
JL
Department of Medicinal Chemistry, Catholic University of Louvain, Brussels, Belgium.
Poupaert
J H
JH
Dumont
P
P
D000284:Administration, Oral; D000818:Animals; D004337:Drug Carriers / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008297:Male; D008314:Malonates / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008854:Microscopy, Electron; D015394:Molecular Structure; D008970:Molecular Weight; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D014018:Tissue Distribution / Q000502:physiology
D004337:Drug Carriers; D008314:Malonates; D011108:Polymers; C068210:poly(diethyl methylidenemalonate); C068209:diethyl methylidenemalonate