尼莫地平/川芎嗪双载药纳米粒的制备及脑内分布研究

何雯洁, 何晓玮, 戴东波, 尤佳, 魏颖慧, 李范珠*

中国药学杂志 ›› 2014, Vol. 49 ›› Issue (6) : 479-484.

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中国药学杂志 ›› 2014, Vol. 49 ›› Issue (6) : 479-484. DOI: 10.11669/cpj.2014.06.011
论 著

尼莫地平/川芎嗪双载药纳米粒的制备及脑内分布研究

  • 何雯洁1, 何晓玮2, 戴东波1, 尤佳1, 魏颖慧1, 李范珠1*
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Preparation and Brain Distribution of NMD/TMP-Loaded PLGA Nanoparticles

  • HE Wen-jie1, HE Xiao-wei2, DAI Dong-bo1, YOU Jia1, WEI Ying-hui1, LI Fan-zhu1*
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文章历史 +

摘要

目的 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(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 5 μg·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。

Abstract

OBJECTIVE To prepare nimodipine/tetramethylpyrazine-loaded poly dual-drug nanoparticles (nimodipine/tetramethylpyrazine-PLGA- nanoparticles, NMD/TMP-PLGA-NPs), and investigate the in vitro release behavior and brain distribution. METHODS NMD/TMP-PLGA-NPs were prepared by optimized emulsion solvent evaporation method with PLGA as a carrier material; the morphology of NMD/TMP-PLGA-NPs was observed by transmission electron microscope; the mean particle size, particle size distribution and Zeta potential were measured by laser particle size analyzer; the entrapment efficiency and drug loading were measured by ultracentrifugation; the in vitro release behavior was studied by dialysis; the brain distribution was compared with NMD-suspension and NMD-PLGA-NPs. RESULTS The NMD/TMP-PLGA-NPs were spherical; the mean particle size, particle size distribution and Zeta potential of NPs were (631.60±3.20) nm, (0.097±0.007), (-29.25±1.87) mV, respectively. The entrapment efficiency and drug loading of NMD were (76.25±1.18)% and (1.24±0.01)%, while those of TMP were (39.30±1.00)% and (6.34±0.11)%, respectively. The profiles of in vitro release had the features of sustained release. The AUC0→t of NMD-suspension, NMD-PLGA-NPs and NMD/TMP-PLGA-NPs were 0.268 3, 0.459 6 and 0.881 5 μg·min·mL-1, and the addition of TMP promoted the reach of highest brain concentration.CONCLUSION NMD/TMP-PLGA-NPs are prepared successfully and show sustained-release in vitro, and the distribution of NMD into brain was increased significantly with the addition of TMP.

关键词

尼莫地平 / 川芎嗪 / 聚乳酸-羟基乙酸共聚物 / 双载药纳米粒 / 脑内分布

Key words

nimodipine / tetramethylpyrazine / PLGA / dual-drug nanoparticle / brain distribution

引用本文

导出引用
何雯洁, 何晓玮, 戴东波, 尤佳, 魏颖慧, 李范珠*. 尼莫地平/川芎嗪双载药纳米粒的制备及脑内分布研究[J]. 中国药学杂志, 2014, 49(6): 479-484 https://doi.org/10.11669/cpj.2014.06.011
HE Wen-jie, HE Xiao-wei, DAI Dong-bo, YOU Jia, WEI Ying-hui, LI Fan-zhu*. Preparation and Brain Distribution of NMD/TMP-Loaded PLGA Nanoparticles[J]. Chinese Pharmaceutical Journal, 2014, 49(6): 479-484 https://doi.org/10.11669/cpj.2014.06.011
中图分类号: R944   

参考文献

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基金

国家自然科学基金资助项目(81274089/H2806);浙江省自然科学基金资助项目(LZ13H280001);浙江省新苗人才计划(67412026)
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