Potential of biopartitioning micellar chromatography as an in vitro technique for predicting drug penetration across the blood-brain barrier
Potential of biopartitioning micellar chromatography as an in vitro technique for predicting drug penetration across the blood-brain barrier
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DOI：
10.1016/j.jchromb.2004.04.004
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发表时间：
2004-08-05
影响因子：
3
通讯作者：
Medina-Hernández, MJ
中科院分区：
文献类型：
--
作者：
Escuder-Gilabert, L;Molero-Monfort, A;Medina-Hernández, MJ
血脑屏障（BBB）被认为是药物转运进入中枢神经系统（CNS）的主要屏障。血脑屏障限制了许多药物从血液到脑的被动扩散。任何特定药物扩散穿过BBB的难易程度主要由药物的分子特征决定，因此可以从其分子结构预测药物的BBB渗透性。生物分配胶束色谱法（BMC），一种在适当的实验条件下使用Brij 35的胶束移动的相的胶束液相色谱法模式，可用于模拟药物分配到生物系统中的过程。药物在BMC中的保留取决于药物的疏水性、电子和空间性质。在本文中，BMC预测的BBB渗透能力的药物表示为脑/血液分布系数（BB）的有用性被证明。多元线性回归（MLR）的BB分配系数数据与BMC保留数据和总摩尔电荷的建议。该模型是使用44种异质性药物，包括中性，阴离子和阳离子化合物。与其他报道的方法来预测血脑屏障渗透性的比较。(C)2004 Elsevier B. V.保留所有权利。
The blood-brain barrier (BBB) is considered to be the main barrier to drug transport into the central nervous system (CNS). The BBB restricts the passive diffusion of many drugs from blood to brain. The ease with which any particular drug diffuses across the BBB is determined largely by the molecular features of drugs, and it is therefore possible to predict the BBB permeability of a drug from its molecular structure. Biopartitioning micellar chromatography (BMC), a mode of micellar liquid chromatography that uses micellar mobile phases of Brij35 in adequate experimental conditions, can be useful in mimicking the drug partitioning process into biological systems. Retention in BMC depends on the hydrophobicity, electronic and steric properties of drugs. In this paper, the usefulness of BMC for predicting the BBB penetration ability of drugs expressed as the brain/blood distribution coefficient (BB) is demonstrated. A multiple linear regression (MLR) model that relates the BB distribution coefficients data with BMC retention data and total molar charge is proposed. The model is obtained using 44 heterogeneous drugs including, neutral, anionic, and cationic compounds. A comparison with other reported methodologies to predict the BBB permeability is also presented. (C) 2004 Elsevier B.V. All rights reserved.