title: Self-assembling PEG-p(CL-co-TMC) copolymers for oral delivery of poorly water-soluble drugs: a case study with risperidone.
abstract: Diblock PEG-p(CL-co-TMC) [methoxypoly(ethylene glycol)-poly(caprolactone/trimethylene carbonate)] copolymers form micelles spontaneously and significantly increase the solubility of poorly water-soluble drugs. The aim of this work was to assess these diblock copolymers as oral drug delivery systems in both in vitro and in vivo experiments using risperidone as a model drug. The permeation of risperidone through Caco-2 cell monolayers showed that the apparent permeation coefficient (Papp) was slightly reduced when risperidone was formulated with the copolymer. Based on the higher apparent drug solubility, the copolymer increased drug flux or the total amount of drug which crossed the Caco-2 monolayers. The Papp of the micelle formulation was higher at 37 degrees C than at 4 degrees C. After oral administration to rats, the pharmacokinetic parameters and the pharmacological effect were evaluated. Time courses of receptor occupancy by risperidone after oral administration were similar when risperidone was encapsulated in PEG-p(CL-co-TMC) micelles or solubilized in an aqueous tartaric acid vehicle. The areas under the curve (AUC) were not significantly different although the maximal concentration (Cmax) was twofold lower with the copolymer. The polymeric micelles of PEG-p(CL-co-TMC) seem to be a good candidate for oral drug delivery of poorly soluble drugs.
authors.affiliation: Université Catholique de Louvain, Department of Pharmaceutical Technology, Avenue Mounier, 73 UCL 7320, 1200 Brussels, Belgium.
authors.forename: Louisa
authors.initials: L
authors.lastname: Ould-Ouali
authors.forename: Marc
authors.initials: M
authors.lastname: Noppe
authors.forename: Xavier
authors.initials: X
authors.lastname: Langlois
authors.forename: Bart
authors.initials: B
authors.lastname: Willems
authors.forename: Paula
authors.initials: P
authors.lastname: Te Riele
authors.forename: Philip
authors.initials: P
authors.lastname: Timmerman
authors.forename: Marcus E
authors.initials: ME
authors.lastname: Brewster
authors.forename: Albertina
authors.initials: A
authors.lastname: Ariën
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018938:Caco-2 Cells; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D007783:Lactones / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D011091:Polyesters; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000737:chemistry; D011108:Polymers / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018967:Risperidone / Q000008:administration & dosage* / Q000737:chemistry; D012995:Solubility / Q000187:drug effects; D014867:Water / Q000737:chemistry
chemical_list: D007783:Lactones; D011091:Polyesters; D011108:Polymers; C410438:TMC-ECL copolymer; D014867:Water; D011092:Polyethylene Glycols; D018967:Risperidone