pH-sensitive amphiphilic triblock copolymers containing ortho ester main-chains as efficient drug delivery platforms

Triblock copolymer PEG-block-poly(ortho ester urethane)-block-PEG (PEG-POEU-PEG) was conveniently prepared via polycondensation reaction between the ortho ester-containing diol and hexamethylene diisocyanate (HDI) at varying reaction time followed by termination with polyethylene glycol monomethyl ether (mPEG). PEG-POEU-PEG could further self-assemble into nano-scaled micelles. Ortho ester degradation in these micelles was significantly accelerated at pH 5.0 due to its pH sensitivity. In vitro drug release profiles showed that only a small amount of the loaded DOX was released in PBS solution at pH 7.4, while DOX could be quickly released at pH 5.0. MTT assay reveals that the micelles were completely nontoxic to cultured cells. Moreover, DOX-loaded micelles exhibited efficient antitumor efficiency against cancer cells. Therefore, the micelles may be potential drug carriers in cancer therapy.