Influence of P-glycoprotein inhibitor on the amphotericin B transport across the blood brain barrier
10.3760/cma.j.issn.1000-6680.2012.08.001
- VernacularTitle:P-糖蛋白抑制剂对两性霉素B血脑屏障转运的作用
- Author:
Ruiying WANG
;
Jiqin WU
;
Kun SHAO
;
Chen JIANG
;
Xuan WANG
;
Jinning LOU
;
Liping ZHU
;
Xinhua WENG
- Publication Type:Journal Article
- Keywords:
P-glycoprotein;
Amphotericin B;
Blood-brain barrier;
In vitro
- From:
Chinese Journal of Infectious Diseases
2012;30(8):449-453
- CountryChina
- Language:Chinese
-
Abstract:
Objective To determine the influence of P-glycoprotein (P-gp) inhibitor on the blood brain barrier (BBB) transport of amphotericin B (AmB)..Methods An in-vitro BBB model was established with brain capillary endothelia cells (BCEC). AmB was chosen as the test drug and verapamil was chosen as the inhibitor of P-gp.Cellular uptake of AmB at different time points and with series of verapamil concentrations were performed respectively after the determination of appropriate incubation time and drug dosage by the cytotoxicity assay. The AmB concentrations of series of samples were detected using high performance liquid chromatography (HPLC) method. One-way ANOVA analysis and Bonferroni test were used for data analysis.Results The cellular transport of AmB was accumulated as the time prolonged.The inhibitor group had a significant higher cellular uptake levelsof AmBat the time point of 90 min (t=6.753,P=0.001),120 min (t=3.574,P=0.016) and 150 min (t=4.759,P=0.005) as compared with the control group.The AmB cellular uptake level increased significantly when BCEC were incubated with verapamil of 2 μmol/L (P=0.000),5 μmol/L (P=0.014),10 μmol/L (P=0.000),50 μmol/L (P=0.014),75 μmol/L (P=0.000) and 100 tμmol/L (P=0.000),respectively,compared with the control group.Conclusion The P-gp inhibitor verapamil can enhance the cellular uptake of AmB which indicates that P-gp is involved in the BBP transport of AmB.
