柔性纳米脂质体的制备及其脑内药物递送效率研究

Study on Preparation of Flexible Nano Liposome and Drug Delivery Efficiency of Brain

关键词:  柔性纳米脂质体  脑靶向  脑源性神经营养因子  稳定性

Key words:  flexible nano liposomes  brain targeting  brain derived neurotrophic factor (BDNF)  stability

摘要:

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。

Abstract:

OBJECTIVE To prepare brain targeting brain derived neurotrophic factor-flexible nano liposome(BDNF-FNL), screening and optimization of preparation process using the brain derived neurotrophic factor (BDNF) as model drug, and to evaluate the quality of preparation. METHODS Intranasal brain targeting drug delivery system of BDNF-FNL were prepared by injection. The evaluation index were the morphology, particle size, entrapment efficiency and Zeta potential. The size distribution of BDNF-FNL were studied that related to influences of stirring temperature, stirring speed and the volume ratio of alcohol to water. And orthogonal design was adopted to obtain the optimal preparation technology based on the influences. Drug brain targeting delivery efficiency of flexible nano liposome was evlauted by determination of BDNF concentration in the brain. RESULTS The results of orthogonal test showed that the best preparation method was as follows: stirring temperature was 30 ℃, stirring speed was 600 r·min^-1 and the volume ratio of alcohol to water was 1∶5. BDNF-FNL were round shape, particle size of (178.7±22.1) nm, and zeta potential of -29.8 mV. The preparation of stable storage for 30 d at 4 ℃, relative humidity (60±10)% conditions. Compared with the BDNF solution group, the group of BDNF-FNL could increase the concentration of BDNF in the brain for nearly 3 times, and the difference between two groups was statistically significant(P<0.05 or P<0.01). CONCLUSION BDNF-FNL prepared in the best process can significantly improve the drug concentration of BDNF in the brain.