Amphiphilic diblock copolymers based on poly(2-ethyl-2-oxazoline) and poly(4-substituted-ε-caprolactone): Synthesis, characterization, and cellular uptake

Abstract

Amphiphilic diblock copolymers with various block compositions were synthesized on poly(2-ethyl-2-oxazoline) (PEtOz) as a hydrophilic block and poly(4-methyl-ε-caprolactone) (PMCL) or poly(4-phenyl-ε-caprolactone) (PBCL) as a hydrophobic block. These PEtOz-b-PMCL and PEtOz-b-PBCL copolymers consisting of soft domains of amorphous PEtOz and PM(B)CL had no melting endothermal peaks but displayed Tg. The lower critical solution temperature (LCST) values for the PEtOz-b-PMCL, and the PEtOz-b-PBCL aqueous solution were observed to shift to lower temperature than PEtOz homopolymers. Their aqueous solutions were characterized using fluorescence techniques and dynamic light scattering (DLS). The block copolymers formed micelles with critical micelle concentrations (CMCs) in the range 0.6–11.1 mg L−1 in an aqueous phase. As the length of the hydrophobic PMCL or PBCL blocks elongated, lower CMC values were generated. The mean diameters of the micelles were between 127 and 318 nm, with PDI in the range of 0.06–0.21, suggesting nearly monodisperse size distributions. The drug entrapment efficiency and drug-loading content of micelles depend on block polymer compositions. In vitro cell viability assay showed that PEtOz-b-PMCL has low cytotoxicity. Doxorubicin hydrochloride (DOX)-loaded micelles facilitated human cervical cancer (HeLa) cell uptake of DOX; uptake was completed within 2 h, and DOX was able to reach intracellular compartments and enter the nuclei by endocytosis. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2769–2781