Synthesis, self-assembly, drug-release behavior, and cytotoxicity of triblock and pentablock copolymers composed of poly(ε-caprolactone), poly(L -lactide), and poly(ethylene glycol)

Abstract

Biocompatible and biodegradable ABC and ABCBA triblock and pentablock copolymers composed of poly(ε-caprolactone) (PCL), poly(L-lactide) (PLA), and poly(ethylene glycol) (PEO) with controlled molecular weights and low polydispersities were synthesized by a click conjugation between alkyne-terminated PCL-b-PLA and azide-terminated PEO. Their molecular structures, physicochemical and self-assembly properties were thoroughly characterized by means of FT-IR, 1H-NMR, gel permeation chromatography, differential scanning calorimetry, wide-angle X-ray diffraction, dynamic light scattering, and transmission electron microscopy. These copolymers formed microphase-separated crystalline materials in solid state, where the crystallization of PCL block was greatly restricted by both PEO and PLA blocks. These copolymers self-assembled into starlike and flowerlike micelles with a spherical morphology, and the micelles were stable over 27 days in aqueous solution at 37 °C. The doxorubicin (DOX) drug-loaded nanoparticles showed a bigger size with a similar spherical morphology compared to blank nanoparticles, demonstrating a biphasic drug-release profile in buffer solution and at 37 °C. Moreover, the DOX-loaded nanoparticles fabricated from the pentablock copolymer sustained a longer drug-release period (25 days) at pH 7.4 than those of the triblock copolymer. The blank nanoparticles showed good cell viability, whereas the DOX-loaded nanoparticles killed fewer cells than free DOX, suggesting a controlled drug-release effect. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem.