The triblock copolymer is composed of two identical hydrophilic segments: Monomethoxy poly(
ethylene glycol) (
mPEG) and one hydrophobic segment poly(ε‑caprolactone) (PCL); which is synthesized by coupling of
mPEG-PCL-
OH and mPEG‑COOH in a mild condition using
dicyclohexylcarbodiimide and 4-dimethylamino
pyridine. The amphiphilic block copolymer can self-assemble into nanoscopic
micelles to accommodate doxorubixin (DOX) in the hydrophobic core. The physicochemical properties and in vitro tests, including cytotoxicity of the
micelles, have been characterized in our previous study. In this study, DOX was encapsulated into
micelles with a
drug loading content of 8.5%. Confocal microscopy indicated that DOX was internalized into the cytoplasm via endocystosis. A dose-finding scheme of the polymeric
micelle (placebo) showed a safe dose of
PEG-PCL-PEG micelles was 71.4 mg/kg in mice. Importantly, the circulation time of DOX-loaded
micelles in the plasma significantly increased compared to that of free DOX in rats. A biodistribution study displayed that plasma extravasation of DOX in liver and spleen occurred in the first four hours. Lastly, the
tumor growth of human
breast cancer cells in nude mice was suppressed by multiple
injections (5 mg/kg, three times daily on day 0, 7 and 14) of DOX-loaded
micelles as compared to multiple administrations of free DOX.