MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
MOE Key Laboratory of Macromolecular Synthesis and Functionalization, Department of Polymer Science and Engineering, Zhejiang University, Hangzhou 310027, China.
Colloids Surf B Biointerfaces. 2015 Jan 1;125:127-33. doi: 10.1016/j.colsurfb.2014.11.017. Epub 2014 Nov 21.
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.
由于小分子与多层膜之间相互作用的限制，难以将其纳入并加以控制，因此，仍然是一个挑战，即控制和刺激小分子从聚电解质多层膜中释放。在此，我们报道了一种简便的方法来制备具有 pH 敏感性的阿霉素（DOX）控制释放的聚电解质多层膜。通过将 DOX 通过 pH 响应腙键接枝到透明质酸（HA）上，将 pH 响应聚电解质接枝到 HA 上，接枝度为 8%。然后，将 HA-DOX 通过聚-L-赖氨酸（PLL）的层层组装掺入多层膜中。通过光谱椭圆术跟踪多层膜的生长。通过扫描电子显微镜和紫外可见光谱分别对薄膜的形态和结构进行了表征。体外药物释放实验表明，DOX 的释放具有 pH 依赖性：在 pH 7.4 时几乎没有释放，而在 pH 6.0 和 5.0 时则明显促进了释放。此外，当用人肝癌（HepG2）细胞在 pH 5.0 下培养时，用（HA-DOX/PLL）多层膜显著抑制了细胞。具有 pH 敏感 DOX 释放性能的多层膜将有可能应用于肿瘤治疗的生物医学装置。
