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目的制备尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]双载药纳米粒(nimodipine/tetramethylpyrazine-PLGA-nanoparticles,NMD/TMP-PLGA-NPs),考察其体外释药特性和脑内分布情况。方法以聚乳酸-羟基乙酸共聚物为载体材料,采用改良的自乳化溶剂挥发法制备尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物双载药纳米粒,正交设计实验优化其处方工艺;透射电子显微镜观察纳米粒形态;激光粒度仪测定其粒径和Zeta电位;高速离心法测定其包封率及载药量;透析袋法考察其体外释药特性;以尼莫地平原料药和尼莫地平聚乳酸-羟基乙酸共聚物纳米粒为对照组,考察大鼠尾静脉注射尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物双载药纳米粒后尼莫地平的脑内分布情况。结果制备的尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物双载药纳米粒外观呈圆形或类圆形,平均粒径为(631.60±3.20)nm,PDI为(0.097±0.007),Zeta电位为(-29.25±1.87)mV,尼莫地平包封率和载药量为(76.25±1.18)%,(1.24±0.01)%,川芎嗪包封率和载药量为(39.30±1.00)%,(6.34±0.11)%;体外释药具有缓释特征;尼莫地平组、尼莫地平聚乳酸-羟基乙酸共聚物纳米粒组和尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物双载药纳米粒组中脑内AUC0→t分别为0.268 3,0.459 6,0.881 5μg·min·mL-1,且加入川芎嗪后尼莫地平更快达到脑内最高浓度。结论本实验成功制备了尼莫地平/川芎嗪聚乳酸-羟基乙酸共聚物双载药纳米粒,其体外释药具有明显缓释特征,加入川芎嗪制备纳米粒可显著提高尼莫地平脑内含量。
OBJECTIVE To prepare nimodipine / tetramethylpyrazine-PLGA nanoparticles (NMD / TMP-PLGA-NPs) for polylactic acid-glycolic acid (PLGA) , Investigate its in vitro release characteristics and brain distribution. Methods Polylactic acid - glycolic acid copolymer was used as carrier material to prepare nimodipine / ligustrazine poly (lactic - co - glycolic acid) copolymer nanoparticles by modified self - emulsifying solvent evaporation method. The orthogonal experimental design was used to optimize its formulation process. Transmission electron microscopy was used to observe the morphology of nanoparticles. The particle size and Zeta potential were measured by laser particle size analyzer. The entrapment efficiency and drug loading were determined by high-speed centrifugation. The in vitro release characteristics were investigated by dialysis bag method. The effect of nimodipine / ligustrazine polylactic acid - glycolic acid copolymer nanoparticle on the brain distribution of nimodipine was investigated. Results The prepared nanoparticles of nimodipine / ligustrazine poly (DL-lactic-co-glycolic acid) double-loaded nanoparticles showed a round or round shape with an average particle size of (631.60 ± 3.20) nm and a PDI of (0.097 ± 0.007) (-29.25 ± 1.87) mV, the entrapment efficiency and drug loading of nimodipine were (76.25 ± 1.18)% and (1.24 ± 0.01)% respectively, the encapsulation efficiency and drug loading of ligustrazine were (39.30 ± 1.00) %, (6.34 ± 0.11)%, respectively. The drug release in vitro showed sustained release characteristics. Nimodipine, nimodipine PLA-NPs and nimodipine / ligustrazine polylactide-glycolic acid bis The AUC0 → t in the drug-loaded nanoparticles group was 0.268 3,0.459 6,0.881 5μg · min · mL-1, and the highest concentration in the brain was reached soon after adding tetramethylpyrazine. Conclusion Nimodipine / ligustrazine poly (DL-lactide-co-glycolide) loaded nanoparticles were successfully prepared in this study. The drug release in vitro was characterized by sustained release. Adding tetramethylpyrazine into the nanoparticles could significantly increase the intramuscular content of nimodipine .