论文部分内容阅读
目的以脑源性神经营养因子(brain derived neurotrophic factor,BDNF)为模型药物,制备脑靶向BDNF柔性纳米脂质体,筛选及优化制备工艺,并对制剂进行质量评价。方法采用注入法制备可经鼻给药的脑靶向柔性纳米脂质体,以外观形态、粒径、包封率和Zeta电位等为评价指标,考察搅拌温度、搅拌速度及醇水比例等因素对BDNF柔性纳米脂质体粒径分布的影响,在此基础上运用正交设计对制备工艺进行优化。通过测定BDNF的脑内药物浓度评价柔性纳米脂质体介导药物脑靶向递送效率。结果正交设计结果表明,搅拌温度30℃、搅拌速度600 r·min-1及醇水比例1∶5为最佳工艺条件,制得的BDNF柔性纳米脂质体形态圆整,粒径为(178.7±22.1)nm,Zeta电位为-29.8 mV。该制剂在温度4℃、相对湿度(60±10)%的条件下贮存30 d稳定。与BDNF溶液组相比,柔性纳米脂质体组能提高BDNF的脑内浓度近3倍,两组间差异具有统计学意义(P<0.05或P<0.01)。结论优化的最佳工艺制得BDNF柔性纳米脂质体可明显提高BDNF的脑内药物浓度。
Objective To prepare brain-targeted BDNF flexible nano-liposomes using brain derived neurotrophic factor (BDNF) as a model drug, and to screen and optimize the preparation process. The quality of the preparations was evaluated. Methods Nasal drug-targeting flexible nanoliposomes were prepared by injection method. The morphology, particle size, entrapment efficiency and Zeta potential were used as evaluation indexes to investigate the effects of stirring temperature, stirring speed and alcohol-water ratio On the BDNF flexible nano-liposome particle size distribution, based on the use of orthogonal design to optimize the preparation process. Flexible nanoliposome-mediated drug-targeted brain targeting delivery efficiency was evaluated by measuring brain drug concentrations of BDNF. Results The results of orthogonal design showed that the optimum conditions were as follows: the stirring temperature was 30 ℃, the stirring speed was 600 r · min-1 and the ratio of alcohol to water was 1: 5. The prepared BDNF flexible nano- 178.7 ± 22.1) nm, and Zeta potential was -29.8 mV. The formulation was stored for 30 days at a temperature of 4 ° C and a relative humidity of (60 ± 10)%. Compared with BDNF solution group, the flexible nanoliposome group could increase BDNF brain concentration nearly 3-fold, the difference between the two groups was statistically significant (P <0.05 or P <0.01). Conclusion The best optimized preparation of BDNF flexible nano-liposomes can significantly increase the intracerebral BDNF drug concentration.