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目的应用Caco-2细胞模型研究5-氟尿嘧啶(5-fluorouracil,5-FU)和卡莫氟(carmofur,HCFU)的渗透性并探讨物理化学性质如logP、pKa值、分子量及水溶性等对两者渗透性的影响。方法实验中应用的5-氟尿嘧啶和卡莫氟的pKa值、水溶性等由文献获得,logP值用HyperChem V5.0软件中的ChemPlus模块计算得到;用跨膜电阻值(transepithelial electricalresistance,TEER)和荧光黄检测细胞完整性,进行渗透实验,计算表观渗透系数(apparent permeability coefficients,P_(app))。结果 5-氟尿嘧啶和卡莫氟的logP值分别为-0.96和2.63;细胞的TEER值维持在760～965 Ω·cm~(-2)之间;荧光黄的P_(app)值为(1.89±0.78)×10~(-7) cm·s~(-1),细胞融合形成了连续的单层细胞膜,且其紧密性和完整性良好;HCFU的P_(app)值约是5-FU的P_(app)值的10倍。结论 logP值对5-氟尿嘧啶和卡莫氟在Caco-2细胞模型中的渗透性起决定作用,5-氟尿嘧啶和卡莫氟的理化特性对两者的渗透性有不同的影响。
Objective To investigate the permeability of 5-fluorouracil (5-FU) and carmofur (HCFU) by Caco-2 cell model and to investigate the physicochemical properties such as logP, pKa, The impact of permeability. The pKa values, water solubility and so on of 5-Fluorouracil and Carmofuril used in the methods were obtained from the literature. The logP values were calculated using the ChemPlus module in HyperChem V5.0 software. The trans-membrane resistance (TEER) and Fluorescent yellow was used to detect the cell integrity. The permeability test was performed to calculate the apparent permeability coefficients (P_ (app)). Results The logP values of 5-fluorouracil and carmofur were -0.96 and 2.63, respectively. The TEER values of cells maintained at 760-965 Ω · cm -2. The app values of fluorescein were 1.89 ± 0.78) × 10 ~ (-7) cm · s ~ (-1). The cells fused to form a continuous monolayer cell membrane with good tightness and integrity. The value of HCFU was about 5-FU 10 times the P_ (app) value. Conclusion The logP value plays a decisive role in the permeability of 5-fluorouracil and carmofur in Caco-2 cell model. The physicochemical properties of 5-fluorouracil and carmofur have different effects on the permeability of both.