Pluronic P85 decreases the delivery of phenytoin to the brain in drug-resistant rats with P-glycoprotein overexpressed chronic mesial temporal lobe epilepsy

被引：2

作者：

Fang, Ziyan ^{[1
,2
,3
]}

Cao, Penghui ^{[1
]}

Pan, Nannan ^{[1
,2
]}

Lu, Haoyang ^{[1
]}

机构：

[1] Guangzhou Med Univ, Affiliated Brain Hosp, 36th Mingxin Rd, Guangzhou 510370, Guangdong, Peoples R China

[2] Guangdong Engn Technol Res Ctr Translat Med Mental, 36th Mingxin Rd, Guangzhou 510370, Guangdong, Peoples R China

[3] Guangzhou Med Univ, Affiliated Brain Hosp, Guangdong Engn Technol Res Ctr Translat Med Mental, Dept Neurol, 36 Mingxin Rd, Guangzhou 510370, Guangdong, Peoples R China

来源：

IBRO NEUROSCIENCE REPORTS | 2023年 / 15卷

基金：

中国国家自然科学基金;

关键词：

Pluronic P85; Tariquidar; P-glycoprotein; Phenytoin; Microdialysis; BARRIER DAMAGE; POLOXAMER; 188; ANTIEPILEPTIC DRUGS; EFFLUX TRANSPORTERS; POLARIZED BBMEC; INHIBITION; PERMEABILITY; MECHANISMS; EXPRESSION; INCREASES;

D O I：

10.1016/j.ibneur.2023.06.009

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

P-glycoprotein (Pgp) overexpressed in blood brain barrier (BBB) is hypothesized to lower brain drug concentrations and thus inhibit anticonvulsant effects in drug-resistant epilepsy. Pluronic P85 (P85) was proved to enhance the delivery of drugs into the brain by inhibition of Pgp. To determine whether the surfactant P85 [versus Pgp inhibitor tariquidar (TQD)] enhance phenytoin (PHT) into the brain in drug-resistant rats with chronic mesial temporal lobe epilepsy (MTLE) induced by lithium-pilocarpine, in brain of which Pgp were overexpressed, then direct verification of PHT transport via measurement of PHT concentration in brain using microdialysis. The drug-resistant model rats were randomly divided into three groups, which were treated with PHT, 1%P85 + PHT, or PHT+TQD, respectively. 1%P85 + PHT treatment displayed a lower ratio of the area under the curve (AUC) of the PHT concentration in the brain/plasma even than that of the PHT treatment in model rats (p < 0.05), while PHT+TQD showed the highest ratio of the AUC of all treatments. However, the ratio of the PHT concentration in the liver/plasma was similar in three model groups (p > 0.05). For the ratio of the kidney/plasma, PHT+TQD treatment model group had the highest ratio of the other treatments in model rats. Thus, P85 oppositely decreased PHT concentration in brain in drug-resistant model rats with Pgp overexpressed MTLE while TQD could increase PHT distribution in brain.

引用

页码：100 / 106

页数：7

共 36 条

[1] Treatment with the non-ionic surfactant poloxamer P188 reduces DNA fragmentation in cells from bovine chondral explants exposed to injurious unconfined compression [J].

Baars, D. C. ;

Rundell, S. A. ;

Haut, R. C. .

BIOMECHANICS AND MODELING IN MECHANOBIOLOGY, 2006, 5 (2-3) :133-139

[2] Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-11C-verapamil and PET [J].

Bankstahl, Jens P. ;

Kuntner, Claudia ;

Abrahim, Aiman ;

Karch, Rudolf ;

Stanek, Johann ;

Wanek, Thomas ;

Wadsak, Wolfgang ;

Kletter, Kurt ;

Mueller, Markus ;

Loescher, Wolfgang ;

Langer, Oliver .

JOURNAL OF NUCLEAR MEDICINE, 2008, 49 (08) :1328-1335

[3] Poloxamer-188 Attenuates TBI-Induced Blood-Brain Barrier Damage Leading to Decreased Brain Edema and Reduced Cellular Death [J].

Bao, Hai-Jun ;

Wang, Tao ;

Zhang, Ming-Yang ;

Liu, Ran ;

Dai, Ding-Kun ;

Wang, Yao-Qi ;

Wang, Long ;

Zhang, Lu ;

Gao, Yu-Zhen ;

Qin, Zheng-Hong ;

Chen, Xi-Ping ;

Tao, Lu-Yang .

NEUROCHEMICAL RESEARCH, 2012, 37 (12) :2856-2867

[4]

Batrakova EV, 2001, J PHARMACOL EXP THER, V299, P483

[5] Pluronic P85 increases permeability of a broad spectrum of drugs in polarized BBMEC and Caco-2 cell monolayers [J].

Batrakova, EV ;

Li, S ;

Miller, DW ;

Kabanov, AV .

PHARMACEUTICAL RESEARCH, 1999, 16 (09) :1366-1372

[6] Effects of pluronic P85 unimers and micelles on drug permeability in polarized BBMEC and Caco-2 cells [J].

Batrakova, EV ;

Han, HY ;

Miller, DW ;

Kabanov, AV .

PHARMACEUTICAL RESEARCH, 1998, 15 (10) :1525-1532

[7] Differential in vivo sensitivity to inhibition of P-glycoprotein located in lymphocytes, testes, and the blood-brain barrier [J].

Choo, Edna F. ;

Kurnik, Daniel ;

Muszkat, Mordechai ;

Ohkubo, Tadashi ;

Shay, Sheila D. ;

Higginbotham, James N. ;

Glaeser, Hartmut ;

Kim, Richard B. ;

Wood, Alastair J. J. ;

Wilkinson, Grant R. .

JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 317 (03) :1012-1018

[8] Surfactant poloxamer 188-related decreases in inflammation and tissue damage after experimental brain injury in rats [J].

Curry, DJ ;

Wright, DA ;

Lee, RC ;

Kang, UJ ;

Frim, DM .

JOURNAL OF NEUROSURGERY, 2004, 101 (01) :91-96

[9] Development of a P-glycoprotein knockout model in rodents to define species differences in its functional effect at the blood-brain barrier [J].

Cutler, Leanne ;

Howes, Colin ;

Deeks, Nigel J. ;

Buck, Tania L. ;

Jeffrey, Phil .

JOURNAL OF PHARMACEUTICAL SCIENCES, 2006, 95 (09) :1944-1953

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

Fang, Ziyan ;

Chen, Shuda ;

Qin, Jiaming ;

Chen, Bao ;

Ni, Guanzhong ;

Chen, Ziyi ;

Zhou, Jueqian ;

Li, Ze ;

Ning, Yuping ;

Wu, Chuanbin ;

Zhou, Liemin .

BIOMATERIALS, 2016, 97 :110-121

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