摘要
目的合成硫酸乙酰肝素-维生素E琥珀酸酯(heparan sulfate-vitamin E succinate,HDV)两亲性材料,包载多柔比星形成聚合物胶束,并对其制剂学性质进行考察。方法通过酰胺反应,合成HDV载体,利用核磁对其结构进行确证。选择超声法制备载多柔比星的聚合物胶束,考察胶束的粒径、形貌、电位、载药量、包封率以及体外释放行为,并对其体外细胞毒性进行了评价。结果成功地合成了HDV两亲性聚合物材料,制备的载药胶束平均粒径为(105.0±7.3)nm,PDI值为(0.239±0.484),电位值为(-21.4±2.6)m V,包封率为(76.22±0.76)%,载药量为(9.53±0.58)%;体外药物释放实验结果表明,载药胶束具有良好的缓释作用。细胞毒性实验显示,空白胶束对正常细胞和肿瘤细胞都几乎没有毒性,而载药胶束具有较好的抗肿瘤活性。结论 HDV聚合胶束可以有效地包载抗肿瘤药物多柔比星,具有良好的缓释特性和抗肿瘤活性,可作为一种潜在应用价值的抗肿瘤药物载体。
OBJECTIVE To prepare heparan sulfate-vitamin E succinate (HDV) amphipathic copolymers and explore the phar- maceutical properties of doxorubicin (DOX) -loaded HDV copolymer micelles ( DOX/HDV ). METHODS HDV copolymers were prepared by amide reaction and its structure was confirmed by i H-NMR. DOX/HDV micelles were prepared by ultrasonic method. The panicle size, morphology, Zeta potential, drug loading, entrapment efficiency, and in vitro drug release and cytotoxicity were evalua- ted. RESULTS HDV amphipathic copolymers were synthesized successfully. The particle size, PDI value and Zeta potential of drug- loaded micelles were (105.0±7.3) nm, (0. 239 ±0. 484) and ( -21.4 ±2.6) mV, respectively. The encapsulation and drug load- ing rate were (76. 22 ±0. 76)% and (9.53 ± 0. 58)%, respectively. The results of drug release test in vitro showed that DOX was released slowly from the micelles. Cytotoxicity experiments indicated that blank micelles had no apparent toxicity against both tumor cells and normal cells. However, DOX/HDV micelles could inhibit the tumor cells growth obviously. CONCLUSION HDV copoly- mers can effectively load DOX with properties of drug sustained release and enhanced cytotoxicity against tumor cells in vitro, which in- dicates that HDV may be a potential candidate for cancer therapy.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2016年第15期1302-1307,共6页
Chinese Pharmaceutical Journal
基金
国家自然科学基金青年科学基金资助项目(81503007)