Pluronic P85-coated poly(butylcyanoacrylate) nanoparticles overcome phenytoin resistance in P-glycoprotein overexpressing rats with lithium-pilocarpine-induced chronic temporal lobe epilepsy

被引：51

作者：

Fang, Ziyan ^{[1
,4
]}

Chen, Shuda ^{[2
]}

Qin, Jiaming ^{[1
]}

Chen, Bao ^{[3
]}

Ni, Guanzhong ^{[1
]}

Chen, Ziyi ^{[1
]}

Zhou, Jueqian ^{[1
]}

Li, Ze ^{[2
]}

Ning, Yuping ^{[4
]}

Wu, Chuanbin ^{[3
]}

Zhou, Liemin ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Affiliated Hosp 1, Dept Neurol, 58th Zhongshan 2nd Rd, Guangzhou 510080, Guangdong, Peoples R China

[2] Guangzhou First Peoples Hosp, Dept Neurol, 1st Panfu Rd, Guangzhou 510180, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

[4] Guangzhou Med Univ, Guangzhou Huiai Hosp, Dept Neurol, Affiliated Brain Hosp, Guangzhou 510370, Guangdong, Peoples R China

来源：

BIOMATERIALS | 2016年 / 97卷

基金：

中国国家自然科学基金;

关键词：

P-glycoprotein; Phenytoin; Microdialysis; Drug resistance; Nanoparticles; Tariquidar; BLOOD-BRAIN-BARRIER; DRUG EFFLUX TRANSPORTERS; N-BUTYL CYANOACRYLATE; 80-COATED POLYBUTYLCYANOACRYLATE NANOPARTICLES; CEREBRAL ARTERIOVENOUS-MALFORMATIONS; IN-VIVO; REFRACTORY EPILEPSY; MULTIDRUG-RESISTANCE; INCREASED EXPRESSION; ANTIEPILEPTIC DRUGS;

D O I：

10.1016/j.biomaterials.2016.04.021

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

P-glycoprotein (Pgp) overexpression in the blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Recently, the poly(butylcyanoacrylate) (PBCA) nanoparticle system was shown to overcome the obstacle of the BBB to deliver drugs into the brain. To determine whether pluronic P85-coated phenytoin poly(butylcyanoacrylate) nanoparticles (P85-PHT-PBCA-NPs) target PHT to the brain, PHT-resistant rats overexpressing Pgp in the BBB were screened by response to PHT treatment after chronic temporal lobe epilepsy induced by lithium-pilocarpine, followed by direct verification of PHT transport via measurement of brain PHT concentrations using microdialysis. Thereafter, the PHT-resistant rats were divided into three groups, which were treated with PHT, PHT + tariquidar (TQD), or P85-PHT-PBCA-NPs. PHT + TQD and P85-PHT-PBCA-NPs showed anticonvulsant activity in the PHT-resistant rats and increased the ratio of the area under the curve of the PHT concentrations in the brain/plasma in comparison with that observed in animals subjected to PHT treatment. However, the ratios of the PHT concentrations in the liver/plasma and kidney/plasma following P85-PHT-PBCA-NPs treatment were much lower than those measured following PHT + TQD treatment. Thus, Pgp overexpression decreases therapeutic drug concentrations in the brains of subjects with drug-resistant epilepsy and P85-PHT-PBCA-NPs could increase these drug concentrations. (C) 2016 Elsevier Ltd. All rights reserved.

引用

页码：110 / 121

页数：12

共 64 条

[1] Delivery of loperamide across the blood-brain barrier with polysorbate 80-coated polybutylcyanoacrylate nanoparticles [J].