载多柔比星透明质酸聚合物胶束的制备及其抗肿瘤活性  

Preparation and Antitumor Activity of Hyaluronic Acid Polymeric Micelles Loaded with Doxorubicin

作　　者：邱立朋[1,2] 龙苗苗[1] 田晨敏 李玲[3] 陈大为[1,3] 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]江南大学药学院,江苏无锡214122 [3]苏州大学药学院,江苏苏州215123

出　　处：《中国医药工业杂志》2016年第3期294-298,322,共6页Chinese Journal of Pharmaceuticals

基　　金：国家自然科学基金面上项目(81173004)

摘　　要：通过超声法制备了载多柔比星的透明质酸-聚组氨酸聚合物(HPH)胶束。结果所得胶束呈类球形,粒径为(212.2±11.9)nm,多分散系数为0.28±0.02,?电位为(-11.91±0.66)m V,包封率为(92.09±0.88)%,载药量为(7.24±0.46)%。体外释放结果显示载药胶束具有明显的p H依赖性。胶束在酸性(p H 5.0和6.0)介质中的释药速度明显高于在中性(p H 7.4)介质中。体外细胞毒性试验表明,空白载体对表面过表达CD44受体的肿瘤细胞MCF-7和A549以及正常细胞L929均无明显毒性;但载药胶束对肿瘤细胞的存活率具有明显抑制作用,且呈浓度依赖性,而即使胶束中1浓度达到10?g/ml,L929细胞的存活率仍接近60%。细胞摄取试验表明,载药胶束在肿瘤细胞中的相对摄取量显著大于正常细胞。The hyaluronic acid-g-poly（L-histidine） polymeric micelles loaded with doxorubicin （1） were prepared with ultrasonic method. The pharmaceutical properties of the micelles were investigated. The particle size, polydispersity index and ζ potential of the micelles with a spherical appearance were （212.2±11.9） nm, 0.28±0.02 and （-11.91±0.66） mV, respectively. The encapsulation efficiency and drug loading were （92.09±0.88） % and （7.24±0.46） %, respectively. The results of the in vitro drug release test demonstrated that 1 released from the micelles in a pH- dependent manner. The release rates of 1 in acidic media （pH 5.0 and 6.0） were higher than in neutral medium （pH 7.4）. In vitro cytotoxicity assays showed that the blank micelles were nontoxic against both MCF-7 and A549 tumor cells （overexpressed CD44 receptors） as well as L929 normal cells. However, the drug-loaded micelles presented a significant inhibitory effect on the two tumor cell lines in a dose-dependent manner, while the viability of L929 ceils was about 60 even if the drug concentration reached up to 10 μg/ml. Cellular uptake experiment revealed that the uptakes of polymeric micelles in turnor cells were significantly more than that in normal cells.

关 键 词：多柔比星 透明质酸 聚组氨酸 P H敏感 CD44受体 

分 类 号：R944.9[医药卫生—药剂学]