肝靶向半乳糖化棕榈酰壳聚糖聚合物胶束作为药物载体的研究-药剂学专业论文.docxVIP

广东药学院硕士研究生学位论文 广东药学院硕士研究生学位论文 I I 肝靶向半乳糖化棕榈酰壳聚糖聚合物胶束作为药物载体的研究 荣利（药剂学） 指导老师：胡巧红 教授 摘 要 聚合物胶束是一种新型的药物载体，由于其具有独特的壳核结构和性质，在纳米给 药系统领域具有广泛的应用前景。本文以具有肝靶向性的两亲性壳聚糖衍生物—半乳糖 化棕榈酰壳聚糖为载体材料制备聚合物胶束，并研究其理化性质和体外抗癌活性。 本文 以本课题组自制的含不同脂肪链取代度的壳聚糖衍生物作为聚合物胶束的载体 材料，采用乳化-溶剂挥发法分别制备聚合物胶束，并 用芘荧光探针法测定聚合物胶束的 临界胶束浓度，筛选出具有合适 CMC值的半乳糖化棕榈酰壳聚糖作为制备载药聚合物胶束 的材料。选择羟基喜树碱为模型药物，采用乳化-溶剂挥发法，以氯仿-乙醇的混合溶剂 溶解药物和载体材料后作为油相，制备载药聚合物胶束。用紫外分光光度法测定载药胶 束的包封率和载药量，在单因素实验的基础上，采用正交设计实验对处方和制备工艺进 行考察，优化后的最佳处方和制备工艺为：药物 /载体比例=0.2:1、油/水相比例=1:7、 超声时间 =40min。采用透射电镜观察载药胶束的形态，粒度检测仪测定粒径及 Zeta电位。 以含 0.02%吐温80的0.1 mol/L pH7.4的PBS 为释放介质，考察载药胶束的体外释放行为， 并分析释药 机制。采用MTT法，考察载药胶束对人肝癌细胞株HepG2细胞的体外生长抑制 作用，并与羟基喜树碱溶液、空白胶束进行比较，结果载药胶束对HepG2细胞的抑制作用 均低于羟基喜树碱溶液， 空白胶束对细胞有较低的 抑制作用。 关键词：聚合物胶束； 壳聚糖； 羟基喜树碱； 乳化 -溶剂挥发法 ；MTT法 II II Study on liver-targeting galactosylated palmitoyl chitosan polymeric micelle s as drug carriers Rong Li (Pharmaceutics) Supervisor: Professor Hu Qiao-hong Abstract As a new drug carrier, polymeric micelles have potential application in nano drug delivery system, because of its unique core-shell structure and properties. In this paper, a hepatocyte-targeting amphiphilic chitosan derivative , galactosylated palmitoyl chitosan, was used as carrier material to prepare polymeric micelles, and its properties and in vitro anti-tumor activity were investigated. Galactosylated palmitoyl chitosans with different degree of substitution of alkyl prepared by our research group were used as carrier material. Polymeric micelles were prepared by emulsifying-solvent evaporation technique . The critical micelle concentrations (CMC) of polymeric micelles were determined by fluorescence spectrophotometry, using pyrene as a hydrophobic probe. Galactosylated palmitoyl chitosan with appropriate CMC was selected as the carrier material for preparing drug-loaded polymeric micelles. Using Hydroxyl camptothecin (HCPT) as model drug and chloroform- methanol mixed solvent as the dissolving medium (als