title: Biodegradable self-assembling PEG-copolymer as vehicle for poorly water-soluble drugs.
abstract: OBJECTIVE
  To develop self-assembling systems increasing the solubility of poorly water-soluble drugs.
  
  
  METHODS
  Low molecular weight liquid biodegradable copolymers were synthesized by ring-opening polymerization using caprolactone (CAP) and trimethylenecarbonate (TMC) as monomers. Various initiators were evaluated. The emulsifying and self-assembling properties were investigated by a water titration method. The self-assembling systems were characterized for size, shape, isotropic behavior, cloud point, surface charge, and critical micellar concentration in order to optimize the polymer synthesis. Finally, the improvement of solubility of model drugs was assessed.
  
  
  RESULTS
  Only diblock monomethyl ether PEG-CAP/TMC copolymers synthesized with monomethyl ether polyethyleneglycol 550 to 2000 as initiator have shown self-assembling properties: upon dilution, these copolymers formed an isotropically clear solution with droplet sizes in the range of 20 to 100 nm. The hypothesis that these diblock polymers form micelles was confirmed by their low critical micellar concentration (10(-5) g/ml). The copolymers initated with mmePEG750 had a higher cloud point and better colloidal stability than those initiated with mmePEG 550. The solubility of the poorly water-soluble drugs was increased by 1 to 2 orders of magnitude. Good reproducibility was observed from batch to batch.
  
  
  CONCLUSIONS
  The polyester diblock copolymer mmePEG750-CAP/TMC forms spontaneously stable micelles in aqueous medium and increases the solubility of lipophilic drugs. They are very promising vehicles for the oral delivery of poorly water-soluble drugs.
authors.affiliation: Université Catholique de Louvain, Department of Pharmaceutical Technology, Brussels, Belgium.
authors.forename: Louisa
authors.initials: L
authors.lastname: Ould-Ouali
authors.forename: Albertina
authors.initials: A
authors.lastname: Ariën
authors.forename: Joel
authors.initials: J
authors.lastname: Rosenblatt
authors.forename: Aruna
authors.initials: A
authors.lastname: Nathan
authors.forename: Patricia
authors.initials: P
authors.lastname: Twaddle
authors.forename: Tom
authors.initials: T
authors.lastname: Matalenas
authors.forename: Maureen
authors.initials: M
authors.lastname: Borgia
authors.forename: Steve
authors.initials: S
authors.lastname: Arnold
authors.forename: Daniel
authors.initials: D
authors.lastname: Leroy
authors.forename: Mustapha
authors.initials: M
authors.lastname: Dinguizli
authors.forename: Laurence
authors.initials: L
authors.lastname: Rouxhet
authors.forename: Marcus
authors.initials: M
authors.lastname: Brewster
authors.forename: Véronique
authors.initials: V
authors.lastname: Préat
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D002208:Caproates / Q000737:chemistry*; D002254:Carbonates / Q000737:chemistry; D004146:Dioxanes / Q000737:chemistry*; D004355:Drug Stability; D004655:Emulsions; D007783:Lactones / Q000737:chemistry*; D008823:Micelles; D008956:Models, Chemical; D015394:Molecular Structure; D014677:Pharmaceutical Vehicles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D018967:Risperidone / Q000737:chemistry; D012995:Solubility; D013500:Surface Tension
chemical_list: D001672:Biocompatible Materials; D002208:Caproates; D002254:Carbonates; D004146:Dioxanes; D004655:Emulsions; D007783:Lactones; D008823:Micelles; D014677:Pharmaceutical Vehicles; D011108:Polymers; D011092:Polyethylene Glycols; C443643:trimethylene carbonate; C121056:caprolactone; D018967:Risperidone