壳聚糖修饰的紫杉醇纳米粒的制备

Preparation of paclitaxel nanoparticles modified with chitosan

目的采用聚丙交酯乙交酯共聚物(PLGA)为载体制备紫杉醇(PTX)纳米粒,并用壳聚糖(CTS)进行修饰以减少纳米粒的突释。方法采用乳化-溶剂挥发法制备PTX-PLGA纳米粒,考察乳化剂及浓度、搅拌器械及功率、PLGA分子量、PTX浓度、PLGA浓度、油/水相对纳米粒粒径、包封率和载药量的影响。将按最优处方制得的纳米粒用CTS修饰,通过激光粒度分析仪、扫描电子显微镜、透射电子显微镜初步研究其特征,并比较修饰前后两种纳米粒冻干粉的体外释药特性。结果优选工艺为:乳化剂为1%聚乙烯醇(PVA),400 W细胞粉碎机超声2 min,PLGA分子量5×104,CPTX=1%,CPLGA=200 mg·mL-1,O/W(1∶10)。制得纳米粒的平均粒径为125 nm,分布均匀,形态圆整,Zeta电位为-11 mV,平均包封率为78.22%,平均载药量为3.72%。用8 mg·mL-1CTS修饰后,纳米粒的平均粒径为142 nm,透射电子显微镜下可见CTS层,Zeta电位为+9.22mV,平均包封率80.11%,平均载药量为3.81%,修饰后纳米粒的突释效应减少。结论所用工艺简单易行,CTS修饰的纳米粒有减小突释效应的作用。

OBJECTIVE To prepare paclitaxel （PTX） nanoparticles with Poly lactide - co - glycolide （ PLGA ）. Nanoparticles were modified with chitosan（CTS） to reduce the burst release. METHODS PTX - PLGA - NPs were prepared by emulsion - solvent evaporation method. The influence of types and concentration of emulsifiers, different stirring apparatus and power, molecular weight of PL- GA, CPTX, CPLGA and ratio of O/W were investigated on the mean size, encapsulation efficiency and diug loading for nanoparticle. The nanoparticles prepared with the optimal prescription were modified with CTS. The properties of nanoparticles were preliminarily studied by a dynamic light scattering, SEM and TEM. Meanwhile, the in vitro release of PTX - PLGA - NPs and CTS - PTX - PLGA - NPs were compared and investigated. RESULTS The optimized preparation process was as follows：the concentration of PVA, PTX and PLGA was 1%, 1% and 200 mg. mL - l, respectively. The ultrasonic power of cell disruptor was 400 W, ultrasonic time was 2 rain, and the ratio of organic phase and water phase was 1 ： 10. The average diameter of PTX- PLGA -NPs was 125 nm, Zeta potential was -11 mV, encapsulation efficiency was 78.22% ,the drug - loading content was 3.72%. The average diameter of PTX - PGLA - NPs modified by CTS（8 mg·mL-1） was 142 nm. Through transmission electron microscope, CTS layer could be observed,Zeta potential of the modified NPs was found to be ＋9.22 mV,encapsulation efficiency was 80.11% ,and the drug - loading content was 3.81%. Burst effect could be reduced after Nanoparticles were modified with CTS. CONCLUSION The preparation process was simple. The nanoparticles with CTS could reduce burst effect.