Add time:08/05/2019         Source:sciencedirect.com

A series of poly(2-ethyl-2-oxazoline)-poly(L-lactide) (PEOz-PLA) diblock copolymers were synthesized by ring-opening polymerization of l-lactide using a monohydroxy terminated PEOz-OH macro-initiator in the presence of stannous octoate as catalyst. The resulting diblock copolymers were characterized by 1H nuclear magnetic resonance and gel permeation chromatography. Self-assembled micelles were prepared using the co-solvent evaporation method in water and in phosphate buffered saline (PBS) at pH 7.4, 6.5 and 5.0. The resulting micelles exhibit different morphologies, such as spherical micelles and worm-like micelles depending on the hydrophilic/hydrophobic balance. Spherical micelles were exclusively observed for PEOz-PLA copolymers with short PLA blocks, whereas co-existence of worm-like and spherical micelles was observed for copolymers with long PLA blocks. The micelle size increases with decreasing pH due to the electrostatic repulsion between PEOz chains resulting from ionization of the tertiary amide groups along PEOz chains. A hydrophobic anti-tumor drug, paclitaxel, was entrapped in PEOz-PLA micelles. High loading efficiency up to 86.7% was obtained for copolymers with long PLA blocks. Drug release was performed in PBS at different pH values. During the 30-day release period, faster release was obtained for copolymers with shorter PLA blocks than for copolymers with longer PLA blocks, at acidic pH than at pH 7.4. It is thus concluded that pH-responsive PEOz-PLA copolymer micellss could be promising as carrier of anti-tumor drugs.

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