叶酸修饰pH响应壳聚糖衍生物胶束的制备及性能表征  

Synthesis and characterization of folate modified pH-responsive micelles of chitosan derivatives

作　　者：樊蓉蓉[1] 郗悦玮 王洁欣[1] 乐园[1] 

机构地区：[1]北京化工大学化学工程学院有机无机复合材料国家重点实验室,北京100029

出　　处：《北京化工大学学报（自然科学版）》2017年第3期26-32,共7页Journal of Beijing University of Chemical Technology(Natural Science Edition)

基　　金：国家"973"计划(2015CB932100)

摘　　要：制备了叶酸(FA)、胆固醇琥珀酸单酯(CHS)共修饰的羟丙基壳聚糖衍生物(CHS-HPCHS-FA),该衍生物在水中能够自组装形成粒径为200~400nm的胶束。研究了疏水片段CHS的取代度对胶束的临界胶束浓度、粒径、载药及释药性能的影响,分析了胶束pH响应控释药物的机理,结果表明,疏水片段取代度高的产物,其临界胶束浓度较低,形成的胶束粒径较小,载药效率较高。体外溶出结果显示,载药胶束在pH5.5条件下释药速率明显比pH7.4条件下更快,体现了pH响应控释药物的效果。体外细胞毒性实验结果表明,胶束的生物相容性较好,且叶酸修饰的载药胶束可增强肿瘤细胞的摄取,细胞毒性明显增大。N-（2-hydroxypropyl） derivative of folate （FA） and cholesteryl hemisuccinate （CHS） conjugated chi- tosan （CHS-HPCHS-FA） have been synthesized. CHS-HPCHS-FA can self-assemble to form 200 -400 nm micelles in aqueous media. The effects of the degree of substitution （DS） of CHS on the critical micelle concentration （CMC） , particle size, drug loading capacity and drug release behaviour were studied. The mechanism of pH-responsive controlled drug release was investigated. The results indicated that CHS- HPCHS- FA micelles with a higher DS of CHS groups showed lower CMC values, smaller size and higher drug loading capacity. The in vitro release studies indicated that pH sensitivity enabled rapid drug release at pH 5.5. Furthermore, the micelles are biocompatible and interact well with cells in vitro. Folate-conjugated micelles could thus enhance drug uptake by tumor cells and lead to increased cytotoxicity.

关 键 词：羟丙基壳聚糖 胆固醇琥珀酸单酯 聚合物胶束 PH响应 叶酸靶向 

分 类 号：O636.1[理学—高分子化学]