Intestinal uptake and biodistribution of novel polymeric micelles after oral administration.
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.
Mathot
Frédéric
F
Université Catholique de Louvain, Department of Pharmaceutical Technology, Avenue E. Mounier 73 UCL 73.20, 1200 Brussels, Belgium.
van Beijsterveldt
L
L
Préat
V
V
Brewster
M
M
Ariën
A
A
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
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