Abstract: In order to enchance the efficacy of antineoplastic drugs targeting and antitumor activity,hyaluronic acid-g-octadecyl conjugates were synthesized and used as vehicles for anti-cancer drugs.Doxorubicin(DOX)-loaded hyaluronic acid-g-octadecyl copolymeric micelles were prepared with ultrasonic method.The pharmaceutical properties of the micelles were investigated.The particle sizes of blank micelles and drug-loaded micelles were(180.7±1.25)nm and(178.3±2.24)nm; zeta potentials were(-21.3±0.25)mV and(-18.1±0.31)mV,respectively.The encapsulation efficiency and drug loading of drug-loaded micelles were(96.1%±0.72%) and(16.1%±1.18%),respectively.In vitro drug release study demonstrated that the cumulative release of DOX was merely about 40% at 72h,indicating that the copolymer micelles presented obvious sustained-release behavior.In vitro cytotoxicity assays showed that the blank micelles were nontoxic against all MCF-7 cells.However,DOX-loaded micelles presented significantly inhibitory effect on the tumor cells in a dose manner.Therefore,hyaluronic acid-g-octadecyl copolymeric micelles exhibited the characteristics of high drug envelopment rate,sustained-release behavior and potent antitumor effect.

Key words: pharmaceutics, hyaluronic acid, doxorubicin, copolymeric micelles, antitumor

摘要： 为了增强抗肿瘤药物的靶向性与抗肿瘤活性，本文制备了透明质酸-十八烷聚合物，用其对阿霉素进行包载，考察其理化性质及体外细胞毒性。合成两亲性透明质酸-十八烷聚合物，利用核磁对其结构进行确证。选择超声法制备载阿霉素的聚合物胶束，考察胶束的粒径、电位、包封率、载药量以及体外释放行为。选择乳腺癌细胞MCF-7为肿瘤细胞模型，考察载药胶束的体外抗肿瘤活性。成功合成了透明质酸-十八烷聚合物。制备的空白胶束和载药的胶束的粒径分别为（180.7±1.25）nm和（178.3±2.24）nm，Zeta电位分别为（-21.3±0.25）mV和（-18.1±0.31）mV。载阿霉素聚合物胶束的包封率为（96.1%±0.72%），载药量为16.1%±1.18%，体外释放行为表明在72h的累计药物释放率仅为40%左右，具有明显的缓释行为。体外细胞毒性结果表明，空白聚合物胶束对肿瘤细胞几乎没有毒性，而载阿霉素的聚合物胶束具有较好的抗肿瘤活性。结论：透明质酸-十八烷聚合物胶束可以有效地包载抗肿瘤药物阿霉素，具有良好的缓释特性和抗肿瘤活性。

关键词: 药剂学, 透明质酸, 阿霉素, 聚合物胶束, 抗肿瘤