pH-sensitive controlled release of doxorubicin from polyelectrolyte multilayers

Controlled and stimulated release of small drug molecules from polyelectrolyte multilayers is still a challenge due to the limitations to incorporate and control the interactions between small molecules and multilayers. Herein we reported a facile method to fabricate polyelectrolyte multilayers with pH-sensitive controlled release of doxorubicin (DOX). A pH-responsive polyelectrolyte was prepared by conjugating DOX onto hyaluronan (HA) via pH-responsive hydrazone bond with an 8% grafting degree. The HA-DOX was then incorporated into the multilayers via the layer-by-layer assembly with poly-L-lysine (PLL). The growth of the multilayers was tracked by spectroscopic ellipsometry. The morphology and structure of the films were characterized by scanning electron microscopy and UV-vis spectroscopy, respectively. The in vitro drug release experiments indicated that the release of DOX was pH-dependent: there was almost no release at pH 7.4, while the releases were significantly promoted at pH 6.0 and 5.0. Furthermore, human hepatoma (HepG2) cells were remarkably inhibited under the conditions at pH 5.0 when they were cultured with the (HA-DOX/PLL) multilayers. The multilayers with the properties of pH-sensitive DOX release would be potentially applied to the biomedical devices for tumor treatments.