Solubilization of hydrophobic drugs by methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymer micelles: theoretical and experimental data and correlations.
The solubilization of five model hydrophobic drugs by a series of micelle-forming, water-soluble methoxy poly(ethylene glycol)-block-polycaprolactone diblock copolymers (MePEG-b-PCL) with varying methoxy poly(ethylene glycol) (MePEG) and polycaprolactone (PCL) block lengths was investigated. Variation of the feed weight ratio of MePEG to caprolactone resulted in the synthesis of copolymers with predictable block lengths. The micelle diameter and pyrene partition coefficient (Kv) were directly related to the PCL block length whereas the critical micelle concentrations (CMC) were inversely related to the PCL block length. The aqueous solubilities of the model hydrophobic drugs, indomethacin, curcumin, plumbagin, paclitaxel, and etoposide were increased by encapsulation within the micelles. Drug solubilization was directly related to the compatibility between the solubilizate and PCL as determined by the Flory-Huggins interaction parameter (chisp). Furthermore, the concentration of solubilized drug was also directly related to the PCL block length.
Letchford
Kevin
K
Faculty of Pharmaceutical Sciences, University of British Columbia, 2146 East Mall, Vancouver, British Columbia, Canada V6T 1Z3.
Liggins
Richard
R
Burt
Helen
H
D008823:Micelles; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
D008823:Micelles; D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol