目的 通过修饰透明质酸(hyaluronic acid, HA)末端合成透明质酸-十八烯共聚物(hyaluronic acid-octadecene,HOY),并包载多柔比星制备聚合物胶束,考察其体外制剂学性质。方法 合成末端巯基化的透明质酸(HA-SH),然后通过麦克尔加成反应与1-十八烯链接;超声法制备载药聚合物胶束,研究其粒径、电位、包封率、载药量及体外释放等性质。结果 成功合成透明质酸-十八烯共聚物,其载药胶束的平均粒径为(237.2±2.7) nm,电位值为(-22.37±0.38) mV,包封率为(89.8±0.011)%,载药量为(5.4±0.007)%,体外释放研究表明,48 h时药物的累计释放率接近70%,具有明显的缓释作用。结论 该实验制备了基于末端修饰透明质酸的聚合物胶束,为后续透明质酸给药系统的研究提供了参考。
Abstract
OBJECTIVE To synthesize hyaluronic acid-octadecene (HOY) copolymers by terminal thiolation modification of hyaluronic acid (HA), prepare doxorubicin-loaded micelles and investigate its pharmaceutical characteristics. METHODS HOY copolymers were synthesized through Michael addition reaction. The doxorubicin-loaded copolymer micelles were prepared with ultrasonic method, then the particle size, Zeta potential, encapsulation efficiency, drug loading efficiency and in vitro release behavior were studied. RESULTS HOY copolymers were synthesized successfully. The particle size and Zeta potential of the drug-loaded micelles were (237.2±2.7) nm and (-22.37±0.38) mV, and the encapsulation efficiency and drug loading rate were (89.8±0.011)% and (5.4±0.007)%, respectively. Moreover, the accumulative release of doxorubicin in vitro was about 70% in 48 h, indicating that the drug was released slowly from the micelles. CONCLUSION This study develops a new micellar system based on terminal modified HA, and provides a reference for the study of HA nanocarrier.
关键词
透明质酸 /
末端修饰 /
多柔比星 /
聚合物胶束
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Key words
hyaluronic acid /
terminal modification /
doxorubicin /
copolymer micelle
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中图分类号:
R944
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