叶酸偶联壳聚糖载多西他赛纳米粒的制备

目的:探索靶向叶酸受体的多西他赛(DTX)纳米粒的制备方法。方法:利用叶酸活性酯与壳聚糖分子上的氨基反应,制得叶酸偶联壳聚糖(FA-CTS);再通过离子交联法,将DTX作为模型药物,制备叶酸偶联壳聚糖载DTX(FA-CTS/DTX)纳米粒。以载药量、包封率、粒径和跨距为指标,采用星点设计-效应面法优化搅拌速率、DTX加入量、壳聚糖-三聚磷酸钠(CTS-STPP)的质量比,并进行验证。利用激光粒度分析仪测定纳米粒粒径大小及分布,在磷酸盐缓冲液中对载药纳米粒进行体外释药试验。结果:最优处方(处方量为2.5 mg)为搅拌速率为1 300 r/min、DTX加入量为0.58μg,CTS-STPP的质量比为5.55。所制备的FA-CTS/DTX纳米粒平均粒径为(232.8±0.43)nm、包封率为(86.74±0.60)%、载药量为(25.29±3.21)%、跨距为0.039±1.02;30 min内累积释药40.22%,随后缓慢释放,24 h内累积释药80.25%。结论:成功制备具有缓释作用的FA-CTS/DTX纳米粒。

Preparation of Docetaxel-loaded Folate-conjugated Chitosan Nanoparticles

OBJECTIVE： To explore the preparation method of Docetaxel （DTX）-loaded folate-conjugated chitosan nanoparticles. METHODS： Folate-conjugated chitosan （FA-CTS） was prepared through amino reaction of folic acid active ester and chitosan molecules; FA-CTS/DTX nanoparticles were prepared with ion cross-linking technique using DTX as model material. Using drug-loading amount, entrapment efficiency, particle size and span as index, central composite design-response surface methodolo- gy was used to optimize stir speed, adding amount of DTX, mass ratio of chitosan-sodium tripolyphosphate （CTS-STPP）. The validation test was repeated. The particle size and size distribution were determined by laser scattering particle analyzer. FA-CTS/DTX nanoparticles release in phosphate buffer in vitro was determined. RESULTS： The optimal formulation （formulation amount of 2.5 mg） was as follows： stir speed at 1 300 r/rain, 0.58 μg DTX, mass ratio of CTS-STPP was 5.55. Mean particle size of FA-CTS/ DTX nanoparticles was （232.8 ± 0.43） nm, entrapment efficiency was （86.74 ± 0.60）% , drug-loading amount was （25.29 ±3.21） % and span was 0.039 ± 1.02. 40.22% of nanoparticles were released within 30 min and then released slowly; accumulative release rate was 80.25% within 24 h. CONCLUSIONS： FA-CTS/DTX nanoparticles with the sustained release effect could be prepared successfully with the method.