石杉碱甲聚乳酸-乙醇酸纳米粒的制备、表征及其小鼠活体成像脑靶向分布

Preparation,characterization and brain targeting efficiency in mice of huperzine A-PLGA nanoparticle

目的制备石杉碱甲(HupA)聚乳酸-乙醇酸共聚物(PLGA)纳米粒,并研究其分布特性。方法以PLGA为载体材料,采用乳化溶剂挥发法,正交实验优化HupA-PLGA纳米粒的制备工艺;透射电子显微镜观察纳米粒形态;激光粒度仪测定平均粒径、粒径分布和Zeta电位;HPLC法测定纳米粒的包封率;并通过小动物活体荧光成像实验对纳米粒在小鼠体内的分布特性进行研究。结果优化条件下制备的纳米粒呈圆形,大小较为均一,平均粒径为(46.49±1.37)nm,多分散指数值为0.31±0.01,Zeta电位为(-38.3±1.56)mV,包封率为(28.45±1.52)%,且工艺重现性好。小动物活体成像实验结果表明该纳米粒可以通过血脑屏障到达脑组织,且具有很好的缓释作用。结论以PLGA为载体的HupA纳米粒具有较小的粒径、良好的缓释性能并能提高脑内药物浓度水平。

Objective To prepare huperzine A （ HupA ） -poly （ lactic-co-glycolic acid ） （PLGA） nanoparticles （ HupA-PLGA- NP） and to study their distribution property in mice. Methods HupA-PLGA-NP were prepared by emulsion solvent evaporation meth- od with PLGA as the carrier material, and the formulations were optimized by orthogonal design test. Nanoparticles were characterized by transmission electron microscopy （ TEM ） and laser particle diameter analyzer. Encapsulation efficiency （ EE ） was detected by HPLC. Distribution of nanoparticles in mice was evaluated by in vivo imaging system. Results The nanoparticles prepared by the opti- mal preparation were uniform spherical particles by TEM. Mean diameter, polydisperse index and Zeta potential of nanoparticles were （46. 49 ± 1.37） nm, （0. 31 ± 0. 01 ） and （ - 38. 3 ± 1.56） mV, respectively. EE was （28.45 ± 1.52） %. The verifying experiments indicated that the repeatibility of the experiment was satisfactory. Results of in vivo imaging confirmed that nanoparticles with the diam- eter of about 50 nm could cross blood-brain barrier into brain and had good sustained-release effect. Conclusion HupA-PLGA-NP are found to have smaller particle size, sustained release of HupA and elevated drug concentration in brain.