Facile synthesis of pH-responsive polymersomes based on lipidized PEG for intracellular co-delivery of curcumin and methotrexate

pH-responsive polymersomes were obtained by self-assembling of a carboxyl-terminated PEG amphiphile achieved via esterification of PEG diacid with PEG40stearate. The obtained vesicular systems had spherical shape and a mean diameter of 70 nm. The pH sensitivity was assessed by measuring the variations of particles mean diameter after incubation in media mimicking the physiological (pH 7.4) or tumor (pH 5.0) conditions, recording a significant increase of the vesicles dimensions at acidic pH. The ability of the polymersomes to carry both hydrophobic and hydrophilic drugs was evaluated by loading the vesicles with curcumin and methotrexate, respectively, obtaining high encapsulation efficiencies and pH-dependent release profiles. The drug-loaded polymeric vesicles exhibited improved cytotoxic potential against MCF-7 cancer cell line and were found to be highly hemocompatible. Finally, cellular uptake experiments on MCF-7 cancer cells were conducted to demonstrate the ability of the designed polymersomes to enhance drug penetration inside the cells. (C) 2018 Elsevier B.V. All rights reserved.