差别性释放两种药物的层层组装聚合物膜  

Layer-by-layer Assembled Polymeric Films for Differential Release of Dual Drugs

作　　者：陈栋栋[1] 陈杰[2] 田华雨[2] 陈学思[2] 孙俊奇[1] 

机构地区：[1]吉林大学超分子结构与材料国家重点实验室,化学学院,长春130012 [2]中国科学院生态环境高分子材料重点实验室,长春应用化学研究所,长春130022

出　　处：《高等学校化学学报》2015年第11期2342-2348,共7页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金(批准号:21225419,21221063)资助~~

摘　　要：基于层层组装技术制备了能够差别性释放2种药物的聚合物复合膜.通过大分子前体药物透明质酸-阿霉素(HA-DOX)与壳聚糖(HACC)的层层组装以及膜内后扩散负载甲氨喋呤二钠盐(MTX)的方法,实现了DOX和MTX 2种药物分子在聚合物膜中的负载.DOX和MTX在癌变组织的酸性环境下具有差别性的释放动力学,MTX在24 h内快速释放,而DOX长效缓释达10 d.细胞实验结果表明,差别性释放的DOX和MTX可有效地抑制癌细胞的增殖.Layer-by-layer（LbL）-assembled polymeric films capable of differentially releasing dual anticancer drugs to achieve synergetie therapeutic effects were fabricated. Doxorubiein （DOX） was first conjugated to hyaluronic sodium（HA） via acid labile hydrazone bonds to produce HA-DOX prodrugs. Then HA-DOX was alternately deposited with 2-hydroxypropyhrimethyl ammonium chloride chitosan（HACC） to produce （HACC/ HA-DOX）n （n is the number of deposition cycle ） film. Methotrexate （MTX） was then loaded into （HACC/HA-DOX） 2o film by a post-diffusion process. MTX was quickly released due to the breakage of its electrostatic interaction with film component HACC. Meanwhile, DOX was released in a sustained manner because of the slow hydrolysis of hydrazine bonds. The synergetic therapeutic effects can be achieved by fast release of cell cycle specific drug MTX to effectively inhibit the proliferation of cancer cells and by sustained release of cell cycle non-specific drug DOX to kill cancer cells. The present study provides a new way for designing polymeric films for controlled release of multiple therapeutic agents.

关 键 词：层层组装 聚合物膜 药物传递 差别性释放 

分 类 号：O631[理学—高分子化学] O636[理学—化学]