title: Spontaneously self-assembled micelles from poly(ethylene glycol)-b-poly(epsilon-caprolactone-co-trimethylene carbonate) for drug solubilization.
abstract: Di-block copolymers composed of polyethylene glycol (PEG) and a second block of (co)polyesters of epsilon-caprolactone (CL) and/or trimethylene carbonate (TMC) were synthesized and characterized. Tin octoate was used as catalyst and polymerization were completed over a period of 24 h with high conversion (> 95%). Self-assembling properties in water were evaluated. All di-block copolymers behave similarly except when PCL served as the second block. Stable crew-cut micelles of about 20 nm were obtained by direct dissolution of the liquid di-block copolymers in water at room temperature. When PCL was present as the second block, no solubilization occurred. Drug encapsulation of poorly water-soluble drugs belonging to biopharmaceutics classification system (BCS) class II (ketoprofen and furosemide) was evaluated. Experimental solubility for these two drugs shows a significant enhancement such that a maximum value of 23.4 mg/ml was obtained for ketoprofen in a 10% w/v micellar solution as compared to 0.14 mg in water. In the case of furosemide, the solubility increased from 0.04 mg/ml in water to about 3.2 mg/ml in a 10% w/v micellar solution. Enzymatic degradation of diblock copolymers was also studied in the presence of Pseudomonas lipase in a phosphate buffer solution (pH 7.4). Results indicated rapid degradation of copolymers containing relatively higher amounts of CL compared to TMC suggesting the potential in vivo degradation.
authors.affiliation: Cordis Corp., Welsh and McKean Roads, Spring House, PA, USA.
authors.forename: Dwan'Isa J P
authors.initials: DJ
authors.lastname: Latere
authors.forename: L
authors.initials: L
authors.lastname: Rouxhet
authors.forename: M E
authors.initials: ME
authors.lastname: Brewster
authors.forename: V
authors.initials: V
authors.lastname: Préat
authors.forename: A
authors.initials: A
authors.lastname: Ariën
mesh_terms: D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002850:Chromatography, Gel; D004339:Drug Compounding; D005079:Excipients / Q000138:chemical synthesis / Q000737:chemistry*; D005665:Furosemide / Q000737:chemistry; D007660:Ketoprofen / Q000737:chemistry; D008049:Lipase / Q000737:chemistry; D008823:Micelles; D011091:Polyesters / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D011549:Pseudomonas / Q000201:enzymology; D012995:Solubility
chemical_list: D002021:Buffers; D005079:Excipients; D008823:Micelles; D011091:Polyesters; C491150:poly(2,2-dimethyltrimethylenecarbonate-co-epsilon-caprolactone)-block-poly(ethylene glycol); D011092:Polyethylene Glycols; D005665:Furosemide; D007660:Ketoprofen; D008049:Lipase