中文摘要：

目的 观察普朗尼克P85修饰的聚氰基丙烯酸正丁酯构建的苯妥英钠纳米粒能否避开颞叶内侧癫痫大鼠模型脑中P糖蛋白（P-glycoprotein,Pgp）的外排作用将苯妥英钠靶向输送到脑组织中。方法 锂-匹罗卡品诱导大鼠形成慢性颞叶内侧癫痫模型。免疫组化检测脑组织中Pgp的表达水平。界面聚合法制备苯妥英钠纳米粒,与普通苯妥英钠比较,观察两组不同给药的模型鼠（苯妥英钠纳米粒组6只,普通苯妥英钠组7只）在给药后30、60、120、180、240、300 min时其脑组织中苯妥英钠的药物分布情况。采用立体定向活体微透析技术采集脑微透析液,高效液相色谱法检测待测标本中苯妥英钠的药物浓度。结果 两组不同给药的模型鼠的脑/血浆的时间药物浓度曲线的曲线下面积比值差异有统计学意义[即苯妥英钠纳米粒组（0.37±0.10,n=6）明显高于普通苯妥英钠组（0.19±0.06,n=7）,P〈0.05]。与正常大鼠相比,模型鼠海马CA1、CA3及DG区Pgp表达上调。结论普朗尼克P85修饰的聚氰基丙烯酸正丁酯纳米粒可显著地提高抗癫痫药物苯妥英钠靶向进入Pgp高表达的颞叶内侧癫痫模型鼠脑中的浓度。

英文摘要：

Objective In order to evaluate that whether Pluronic P85 coated poly（butylcyanoacrylate） nanoparti-cles was able to deliver antiepileptic drug phenytoin into the brain va bypassing mesial temporal lobe epilepsy （MTLE）-induced Pgp in a rat model of MTLE. Methods The rat model of MTLE, induced by li-pilocarpine, was divided in-to two groups （6 for nanoparticle drug group and 7 for PHT drug group）. Immunohistochemistry assay was performed to detect Pgp expression at the hippocampus. Nanoparticles were prepared by interfacial polymerization method. Dialysate samples of brain were collected at 30, 60, 120, 180, 240 and 300 min after drug administration by microdialysis tech-nology. Samples were analyzed by high performance liquid chromatography （HPLC）. Results The area under the curve （AUC） ratio of brain/plasma in Nanoparticle drug group was 0.370.10 which was significantly higher compared with 0.190.06 in conventional PHT drug group （P〈0.05）. The Pgp immunopositive area, as assessed by analysis of labeled surface area, was higher in the DG, CA3 and CA1 sector in the hippocampus of MTLE rats when compared to the normal rats. Conclusions Pluronic P85 coated PBCA nanoparticles can significantly deliver PHT into brain via bypassing MTLE-induced Pgp in a rat model of MTLE.