基于Caco-2细胞模型研究FGFC1吸收和转运的特性  

Absorption and transportation characteristics of FGFC1 in Caco-2 cell monolayer

作　　者：王格[1] 严婷[1] 傅诗情 吴文惠[2,3] 张朝燕[1] 包斌[1,2] 

机构地区：[1]上海海洋大学食品学院,上海201306 [2]上海水产品加工与贮藏工程技术研究中心,上海201306 [3]上海海洋大学海洋科学研究院,上海201306

出　　处：《中国新药杂志》2016年第9期1040-1045,共6页Chinese Journal of New Drugs

基　　金：国家高技术研究发展计划(2011AA09070109);国家自然科学基金(81341082)

摘　　要：目的:研究纤溶化合物FGFC1在Caco-2细胞模型中的吸收和转运特性。方法:以跨膜电阻值(transepithelial electrical resistance,TEER)值、阳性对照药荧光黄和普萘洛尔的表观渗透系数(the apparent permeability coefficients,Papp)值来评价模型的完整性、紧密性和通透性。通过LC/MS/MS考察浓度为0.5~5μmol·L-1的FGFC1溶液所产生的外排比、总回收率和表观渗透系数来评价药物的转运特性。结果:本实验培养的Caco-2细胞显示出优良的完整性、紧密性和通透性。在AP→BL方向的总回收率是(35.778±1.285)%^(52.336±4.342)%,在BL→AP方向的总回收率是(25.485±1.131)%^(53.022±2.011)%,AP→BL方向和BL→AP方向的Papp值均小于2.5×10-6cm·s-1,在AP→BL方向的外排比率是(8.745±0.155)%^(26.759±1.024)%,在BL→AP方向的外排比率是(25.549±1.551)%^(52.421±2.203)%。结论:FGFC1不是P-gp的底物。0.1%BSA能明显提高回收率和改善特异性吸附。FGFC1在Caco-2细胞模型中以被动扩散为主。FGFC1低渗透率的研究结论显示出静脉注射给药途径较口服给药途径更为恰当。Objective： To investigate the absorption and transportation characteristics of FGFC1 in the human Caco-2 cell monolayer model. Methods： The integrity,tightness,and permeability of the model were estimated with TEER and the Pappof the lucifer yellow and propranolol. The transportation characteristics was evaluated by Papp,efflux ratio,and the mean total recoveries of FGFC1 at concentration of 0. 5 - 5 μmol·L- 1with LC / MS /MS. Results： The integrality of cell monolayer and the Pappof the blank group in the Caco-2 cell monolayer were satisfactory. The total recoveries were（ 35. 778 ± 1. 285） % -（ 52. 336 ± 4. 342） % and（ 25. 485 ± 1. 131） % -（ 53. 022 ± 2. 011） % at the AP→BL and BL→AP directions,respectively. The PappAP→BL and PappBL→AP were both below 2. 5 × 10^- 6cm·s^- 1. The efflux ratio at the AP→BL direction was（ 8. 745 ± 0. 155） % -（ 26. 759 ±1. 024） %,and that at the BL→AP direction was（ 25. 549 ± 1. 551） % -（ 52. 421 ± 2. 203） %. Conclusion： FGFC1 is not a substrate of P-gp. When 0. 1% BSA was added,the total recoveries and specific absorption were improved significantly. Passive diffusion is the major absorption pattern of FGFC1 in Caco-2 cell model. The low penetrability of FGFC1 indicated that intravenous administration is more appropriate than oral administration for this agent.

关 键 词：FGFC1 CACO-2细胞 表观渗透系数 外排比 总回收率 

分 类 号：R96[医药卫生—药理学]