葡萄糖响应苯硼酸接枝壳聚糖盐酸盐抗肿瘤药物载体  

Glucose Responsive Phenylboric Acid Grafted Chitosan Hydrochloride for Anti-tumor Drug Delivery

作　　者：张雅娟[1] 郑静霞[1] 李娟[1] 胡炜琼 孙云雨[1] 梁洪泽[1] 赵玲玲[1] 梁福鑫[2] 

机构地区：[1]宁波大学材料科学与化学工程学院,宁波315211 [2]中国科学院化学研究所,北京100190

出　　处：《高分子学报》2015年第9期1020-1027,共8页Acta Polymerica Sinica

基　　金：国家自然科学基金(基金号51403108);浙江省自然科学基金(基金号LQ13B040001);北京分子科学国家实验室开放基金;宁波市自然科学基金(基金号2013A610091);宁波大学学科基金(基金号XYL14013;XKZSC05);宁波大学水产浙江省重中之重一级学科开放基金和宁波大学王宽诚幸福基金资助项目

摘　　要：通过分子改性向壳聚糖盐酸盐高分子链中引入苯硼酸基,合成了双亲性化合物苯硼酸接枝壳聚糖盐酸盐.细胞毒性实验表明苯硼酸接枝壳聚糖盐酸盐具有良好的细胞相容性.该双亲性化合物能够自组装成胶束聚集体,并包封疏水药物.以阿霉素为模型药物,研究了载药胶束聚集体的体外药物释放行为,结果表明,阿霉素在载药胶束聚集体内能够持续释放,且具有葡萄糖响应性.在生理p H=7.4和固体肿瘤弱酸性(p H=6.5)条件下,药物的释放速度十分缓慢,而当释放介质中有葡萄糖存在时,药物释放速度都明显加快.Phenylboronic acid grafted chitosan hydrochloride（ HCSPBA） was synthesized by introducing phenylboronic groups to the polymer chain of chitosan hydrochloride through simple molecule modification by the reaction between the amine group of chitosan hydrochloride and the carboxyl group of 3-carboxyphenylboronic acid. The structure of the amphipathic compound was confirmed by FTIR and1H-NMR,and the graft ratio of phenylboronic can be tuned by changing the feed ratio. The cytotoxicity of the HCSPBA was assessed using CCK-8 assay,and the result showed good cytocompatibility. Hydrophobic drugs can be encapsulated to the assembled polymeric micelles of HCSPBA,and showed sustained and controllable release.Herein,doxorubicin was selected as model drug,and the drug release behavior has good glucose responsibility.Without glucose,the cumulative release rate was very low at physiological p H = 7. 4 and weak acidity（ p H =6. 5） condition of solid tumor,while the rate was accelerated when glucose was present in the medium,due to the swelling / disruption of the HCSPBA micelles as a result of the better hydrophilicity of the compound after the combination of phenylboronic group and glucose. Since the high glucose concentration physiological microenvironment of diabetes and solid tumor tissue,the HCSPBA has potential application in developing glucose responsive drug delivery systems,such as smart insulin and anti-tumor drug delivery systems.

关 键 词：苯硼酸 壳聚糖盐酸盐 葡萄糖响应 药物释放 

分 类 号：TQ460.1[化学工程—制药化工]