title: Intestinal uptake and biodistribution of novel polymeric micelles after oral administration.
abstract: To determine the fate of polymeric micelles after oral administration, we investigated the possible transport of polymeric micelles across Caco-2 monolayers and their biodistribution in rats after per os administration of [14C]-labelled mmePEG750P(CL-co-TMC) micelles containing risperidone (BCS Class II drug). mmePEG750P(CL-co-TMC) was able to cross Caco-2 monolayer via a saturable transport mechanism. The oral bioavailability of the polymer was 40%. Polymeric micelles based on mmePEG750P(CL-co-TMC) showed very low clearance by the reticuloendothelial system (RES) and a renal excretion. A sustained release of risperidone was observed.
authors.affiliation: Université Catholique de Louvain, Department of Pharmaceutical Technology, Avenue E. Mounier 73 UCL 73.20, 1200 Brussels, Belgium.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Mathot
authors.forename: L
authors.initials: L
authors.lastname: van Beijsterveldt
authors.forename: V
authors.initials: V
authors.lastname: Préat
authors.forename: M
authors.initials: M
authors.lastname: Brewster
authors.forename: A
authors.initials: A
authors.lastname: Ariën
mesh_terms: D000284:Administration, Oral; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D001692:Biological Transport; D018938:Caco-2 Cells; D002250:Carbon Radioisotopes; D020895:Enterocytes / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007555:Isoxazoles / Q000097:blood; D007668:Kidney / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008823:Micelles; D012157:Mononuclear Phagocyte System / Q000378:metabolism; D000068882:Paliperidone Palmitate; D011091:Polyesters / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011743:Pyrimidines / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D018967:Risperidone / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D014150:Antipsychotic Agents; D002250:Carbon Radioisotopes; D007555:Isoxazoles; D008823:Micelles; D011091:Polyesters; D011108:Polymers; D011743:Pyrimidines; C513506:monomethyletherpoly(oxyethylene glycol(750))-poly(caprolactone-co-trimethylene carbonate); D011092:Polyethylene Glycols; D018967:Risperidone; D000068882:Paliperidone Palmitate