聚氰基丙烯酸正丁酯纳米粒与维拉帕米对苯妥英钠脑靶向分布的比较.pdf

自求恩医学杂志2016年4月第14卷第2期 Journal of Bethune Medical Science Vol_14,No2,Apil,2016
论著
聚氰基丙烯酸正丁酯纳米粒与维拉帕米
对苯妥英钠脑靶向分布的比较
陈树达,黄华锰,邓丽芬,李泽,潘小平,周?情,周列民
[摘要]目的筛选抗癲痫药物苯妥英钠( Phenytoin,PHT)的纳米药物载体构建工艺,并比较纳米粒与P糖蛋白拮抗剂
(P- glycoprotein,PgPp)维拉帕米( Verapamil,VPM)对PHT的脑靶向分布作用。方法分别应用乳化聚合法和界面聚合法构建
PHT聚氰基丙烯酸正丁酯纳米粒,添加1%的普郎尼克P85进行修饰,并进行体外特征鉴定;20只雌性SD大鼠,随机分为
PHT组、PHT+VPM组(添加维拉帕米)、 Cmulsion Nano组(纳米粒由乳化聚合法合成)和 Interfacial Nano组(纳米粒由界面聚
合法合成)。4组给予PHT后分别在不同时间点取大脑微透析液和血液,最后处死大鼠分离肝脏和肾脏组织。高效液相色谱
法检测各样本中苯妥英钠的浓度,苯妥英钠透过血脑屏障的转运率用脑组织间液时间药物浓度曲线的曲线下面积与血浆时
间药物浓度曲线的曲线下面积的比值进行评估;苯妥英钠在外周组织的累积分布情况用给药300min的肝脏/肾脏苯妥英钠
药物浓度与血浆药物浓度的比值进行评估。结果界面聚合法合成的纳米粒较乳化聚合法具有较高的载药量和包埋率,而
平均粒径和Zea电位相近; Interfacial Nano组、 Emulsion Nano组、PHT+VPM组与PHT组比较,脑组织间液和血浆苯妥英钠的
曲线下面积比值分别提高了60.70%(P<0.01)、27.44%(P<0.05)和26.91%(P<0.05); Interfacial Nano组苯妥英钠药物浓
度肝血比和肾血比明显下降,PHT+VPM组肝血比和肾血比明显升高,与PHT组比较差异均有统计学意义(P<0.05)。Emul-
sion Nano组与PHT组相近,差异无统计学意义。结论界面聚合法纳米粒制备工艺相对优于乳化聚合法。相对于VPM,添
加1%的普郎尼克P85修饰的界面聚合法制备的纳米粒可明显提高PHT在脑组织中的分布,具有脑靶向输送作用。
[关键词」普朗尼克P85;维拉帕米;聚氰基丙烯酸正丁酯纳米粒;微透析;脑靶向分布
[中国图书资料分类号]R9%[文献标志码]A[DOI]10.16485/j.jisa.2095-7858.2016.02.001
Efect of PBCA-NPS on PHT targeted distribution in brain vs VPM
CHE Shuda, HUANG Huameng, DENG Lifen, et al. Guangzhou First Peoples Hospial, Guangdong 510180, China
Abstract] Objective Screening manufacture process of nano drug carrier of traditional antiepileptic drugs phenytoin, and at-
tempt to explore the effect of nanopartices on rai ar eted distibution of peny oin mpared with one of antagonists of P-gly oprotein
verapamil. Methods Constructing pheny oin polyu le anoacr late nanoparticles respectively by emulsion and interfacial polymeriz
tion method modifed with 1% luron P5, and ient caion the cancerization in w; SD rats were randomly divided into PHT
group PHT+VPM group, Emulsion nano group and Interfacial nano group. Several dialysate and blood samples of different times were
c o llected after PHT administration. liver and kidney were removed for tissues distribution study. Concentrations of P T of different sam-
ples were detected by high performance liquid chromatography( HPLC) Ratio of area under curve(AUC )of time drug concentration
curve of brain extracellular fluid and plasma of phenytoin was used to evaluate the brain distribution of phenytoin. Ratio of concentra
tion of phenytoin of live /kidney and plasma at 300 min time-point was used to evaluate accumulation and distribution of phenytoin in
peripheral tissues Results Ineac al polymerization method had higher load quantity and package embedding rate, and similar aver-
age particle size and zeta potential, relative o emulsion pol me zat on method; Compared with the PHT group, the PHT AUC ratios
between brain extracellular fluid and plasma in Interfacial nano group, Emulsion nano group and PHT +VPM group, were significantly
increased by 60. 70%(P<0.01) 27 44%(P<0.05) and 26. 91%(P<0.05), respectively; The hepatic blood ratio and renal
blood ratio of Interfacial nano group decreased significantly(P<0. 05) while those of PHT+VPM group increased significantly(P<
00),omae wt h PHT ou The dienes of Emul on an gu and PHT group were not statistically significant Conclusion
Manufacture process of interfacial polymerization method for nano
基金项目:广东省医学科研基金立项课販(编号:B20135)muhu么 Is relatively better than the emulsion polymerization
基金项目:广