Micellar carriers based on block copolymers of poly(e-caprolactone) and poly(ethylene glycol) for doxorubicin delivery

Diblock copolymers of poly(epsilon-caprolactone) (PCL) and monomethoxy poly(ethylene glycol) (MPEG) with various compositions were synthesized. The amphiphilic block copolymers self-assembled into nanoscopic micelles and their hydrophobic cores encapsulated doxorubicin (DOX) in aqueous solutions. The micelle diameter increased from 22.9 to 104.9 nm with the increasing PCL block length (2.5-24.7 kDa) in the copolymer composition. Hernolytic studies showed that free DOX caused 11% hemolysis at 200 mug ml(-1), while no hemolysis was detected with DOX-loaded micelles at the same drug concentration. An in vitro study at 37 degreesC demonstrated that DOX-release from micelles at pH 5.0 was much faster than that at pH 7.4. Confocal laser scanning microscopy (CLSM) demonstrated that DOX-loaded micelles accumulated mostly in cytoplasm instead of cell nuclei, in contrast to free DOX. Consistent with the in vitro release and CLSM results, a cytotoxicity study demonstrated that DOX-loaded micelles exhibited time-delayed cytotoxicity in human MCF-7 breast cancer cells. (C) 2004 Elsevier B.V. All rights reserved.