两亲性纳米胶束聚乙二醇接枝壳聚糖偶联脱氧胆酸-姜黄素的制备与评价

目的 合成聚乙二醇接枝壳聚糖偶联脱氧胆酸(mPEG-CS-DA)纳米载药系统,并以姜黄素(Cur)为模型药物,构建两亲性纳米胶束,并对其进行理化表征。方法 采用两步反应合成mPEG-CS-DA,分别用IR、¹H-NMR等技术对其结构进行表征,用差示扫描量热法(DSC)对其物理性质进行分析,并考察其在不同溶剂中的溶解性能。筛选mPEG-CS-DA-Cur纳米胶束制备方法,并测定其包封率、载药量、粒径分布及体外释放度。结果 以透析法制备的载药纳米胶束具有较高的包封率,较小的平均粒径和无残留溶剂的特点。mPEG-CS-DA-Cur的载药量为(12.11±1.52)%,包封率为(89.37±4.12)%,平均粒径为161.4 nm,分布均匀,胶束中药物体外释放缓慢、稳定。结论 研究合成了1种新型的两亲性壳聚糖衍生物,是1种良好的胶束载体材料,对难溶性药物Cur具有很好的包封率和载药量,为后续药物进行靶向性研究提供了一定的基础。

Preparation and Evaluation of Amphiphilic Curcumin-Polyethylene Glycol-Grafted Chitosan Coupled with Deoxycholic Acid Micelles

OBJECTIVE To synthesize the polyethylene glycol(mPEG)-grafted chitosan coupled with deoxycholic acid, and to prepare the curcumin-loaded micelles and characterize their physicochemical properties. METHODS mPEG-chitosan-deoxycholic acid was synthesized by two steps, and its structure was characterized by IR, ¹H NMR and the physical properties were charaterized by differential scanning calorimetry(DSC).The solubility of carrier was investigated in various solvents, and the solubilization capacity for insoluble drugs was also discussed.The preparation method of mPEG-CS-DA-Cur micelles was optimized, and the entrapment efficiency, drug loading, particle size distribution and drug release behavior were also characterized. RESULTS The drug-loaded nano-micelles prepared by dialysis method have the characteristics of high entrapment efficiency, small average particle size and no residual solvent,the drug loading of mPEG-CS-DA-Cur micelles was(12.11±1.52)%, the encapsulation efficiency was(89.37±4.12)%, and the average particle size was 161.4nm with uniform distribution .The drug release from the micelles was relativley slow and stable. CONCLUSION A new type of chitosan derivative with amphiphilic charateristics is synthesized in this study,and it will be an excellent micelle carriers. It shows high encapsulation efficiency and drug loading for curcumin,which provides a certain references for the follow-up drug targeting research.