以聚氰基丙烯酸正丁酯为载体长春碱纳米粒的制备和性能评价及其对大鼠C6脑神经胶质瘤细胞生长的影响

Preparation and efficiency of Vinblastine Sulfate Nanoparticles loaded by poly(butyl cyanoacrylate) and its effects on the growth of C_6 intracerebral glioma cells in rats

背景：长春碱纳米粒不仅化学特性改善，药物利用度提高，而且具有特异的靶向性。目的：制备硫酸长春碱聚氰基丙烯酸正丁酯纳米粒（vinblastine sulfate poly（butyl cyanoacrylate）NP，VBL-PBCA-NP）并进行质量评价，柃测其对大鼠C6脑胶质瘤细胞的生长抑制作用。设计、时间及地点：随机对照细胞实验，于2006-10／2007-12在西北农林科技大学动物医学院细胞生物学实验窒完成。材料：以右旋糖酐为稳定剂，在pH2.0的条件下，利用乳化聚合法制备VBL-PBCA-NP。方法：取对数生长期的C6大鼠胶质瘤细胞，分别加入0．5，5，50，500，5000μg／L的VBL-PBCA-NP或硫酸长春碱，同时设阴性对照组（加入完全培养基）和空白对照组（只加入完全培养基，不含细胞）及空白纳米粒组。主要观察指标：VBL-PBCA-NP纳米粒的外观形态、粒径、包封率及载药量：C6细胞的增殖抑制率及凋亡形态。结果：VLB-PBCA-NP分布均一，稳定，平均粒径为74．4nm，粒径分布较窄，包封率为74．47％，载药量为18．62％。与硫酸长春碱原料药相比，在0.5～5000μg／L范围内，VBL-PBCA-NP能显著提高C6细胞的增殖抑制率（P〈O．05），且更容易引起C6细胞凋亡，减少细胞数量。结论：制备的VBL-PBCA-NP载药量和包封率不是很高，但对大鼠C6脑神经胶质瘤细胞有较强的生长抑制作用。

BACKGROUND： Vinblastine Sulfate Nanoparticles can not only improve the chemic character, but also increase the usage rate and has specific target. OBJECTIVE： To prepare poly（butyl cyanoacrylate） （PBCA） nanoparticles loaded with Vinblastine Sulfate （VBL-PBCA-NP） and to investigate its anti-carcinoma effect on C6 rat intracerebral glioma cells, DESIGN, TIME AND SETTING： The randomized controlled cell experiment was performed at the Laboratory of Cell Biology of College of Veterinary Medicine, Northwest A＆F University from October 2006 to December 2007. MATERIALS： VBL-PBCA-NP was prepared by emulsification polymerization with dextran as a stabilizing agent under pH 2.0 condition. METHODS： C6 rat glioma cells at logarithmic growth phase were incubated in VBL-PBCA-NP of 0.5, 5, 50, 500, 5 000 μ g/L or Vinblastine Sulfate. There were negative control group （complete medium）, blank control group （complete medium, without cells） and blank nanoparticle group MAIN OUTCOME MEASURES： Shape, size, distribution, entrapment efficiency and loading efficiency of VBL-PBCA-NP; inhibitory effect of VBL-PBCA-NP on proliferation of C6 glioma cells and cell apoptosis. RESULTS： The mean diameter of VLB-PBCA-NP was about 74.4 nm, and drug entrapment efficiency and loading efficiency was 74.47% and 18.62%. Compared with VBL, growth-inhibiting of VBL-PBCA-NP enhanced significantly on C6 rat intracerebral glioma cells （P 〈 0.05） in the area of 0,5-5 000 μ g/L, which easily induced C6 cell apoptosis and decreased cell number. CONCLUSION： Drug entrapment efficiency and loading efficiency are not very high. However, VBL-PBCA-NP can significantly restrain the growth of C6 rat intracerebral glioma cells.