title: Solubilization of sagopilone, a poorly water-soluble anticancer drug, using polymeric micelles for parenteral delivery.
abstract: Polymeric micelles were studied as a drug delivery system for Sagopilone, a poorly water-soluble anticancer drug, with respect to passive tumour targeting. Poly(ethylene glycol)-b-Poly(lactide) (PEG-b-PLA) and Poly(ethylene glycol)-b-Poly(epsilon-caprolactone) (PEG-b-PCL) were investigated to identify suitable copolymers and to assess the predictive value of solubility parameters. The impact of copolymer compositions (different hydrophobic/hydrophilic-ratios (w/w) from 0.3 to 1.3) and the preparation method (sonication; film formation) on the solubilization efficiency, size characteristics and micelle stability were studied. Thermal analysis was used to determine the apparent solid-state solubility. PEG(2000)-b-PLA(2200), PEG(2000)-b-PCL(2600) and PEG(5000)-b-PCL(5000) were identified as the most suitable delivery systems for Sagopilone. They exhibited efficient solubilization (> or =70%) yielding small (<100 nm), monodisperse, and spherical micelles. (80+/-12), (93+/-0.4) and (96+/-6)% of the drug still remained solubilized after 24h, respectively. Calculated solubility parameters were not predictive since they showed a reversed order of preference relative to experimental data. High solubilization after film hydration was accompanied with a 'supersaturation'. The reason for this well-known effect and the solubilization of Sagopilone within the block copolymer was elucidated by the evidence of glass solutions exceeding the solubilization capacity of the corresponding micelles. Overall, micellar drug delivery systems for Sagopilone were identified offering the potential for an improved cancer therapy.
authors.affiliation: Pharmaceutical Technology, Bayer Schering Pharma AG, Muellerstr. 178, 13353 Berlin, Germany.
authors.forename: Annett
authors.initials: A
authors.lastname: Richter
authors.forename: Carsten
authors.initials: C
authors.lastname: Olbrich
authors.forename: Michael
authors.initials: M
authors.lastname: Krause
authors.forename: Thomas
authors.initials: T
authors.lastname: Kissel
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry; D052160:Benzothiazoles / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems; D034261:Epothilones / Q000008:administration & dosage* / Q000737:chemistry; D007783:Lactones / Q000737:chemistry; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D000970:Antineoplastic Agents; D052160:Benzothiazoles; D034261:Epothilones; D007783:Lactones; D008823:Micelles; D011091:Polyesters; D011108:Polymers; C521904:poly(ethylene glycol)-block-poly(epsilon-caprolactone); D011092:Polyethylene Glycols; C033616:poly(lactide); C530494:sagopilone