Solubilization of Sagopilone, a poorly water-soluble anticancer drug, using polymeric micelles for parenteral delivery

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-PCL2500 and PEG(5000)-b-PCL5000 were identified as the most suitable delivery systems for Sagopilone. They exhibited efficient solubilization (>= 70%) yielding small (<100 nm), monodisperse, and spherical micelles. (80 +/- 12), (93 +/- 0.4) and (96 +/- 6)% of the drug still remained solubilized after 24 h, 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. (C) 2010 Elsevier B.V. All rights reserved.