锆镁磷脂膜色谱固定相的制备及其在评价药物-膜相互作用中的应用

Preparation of magnesia-zirconia based mimetic biomembrane stationary phase and its applications in evaluating drug-membrane interactions

基于锆基质与磷脂之间强烈的路易斯酸碱作用,制备了锆镁磷脂膜色谱固定相,并使用红外光谱、X射线光电子能谱对该色谱固定相进行了表征;使用与体内环境类似的生理缓冲液体系为流动相,评价了该模拟生物膜色谱固定相预测药物膜渗透性的能力,结果表明药物在锆镁磷脂膜色谱中的保留(logKmbm)与表观渗透率(logPapp)在预测药物的膜渗透性、跨膜吸收等方面具有非常好的相关性,相关系数为0.970,斜率接近1。通过理论推导,引入了直观、方便的热力学指标吉布斯自由能差值(Δ(ΔG°))对药物-膜之间的相互作用强弱进行了评价。

A novel mimetic biomembrane chromatographic stationary phase of magnesia-zirconia composite matrix was prepared based on the Lewis acid-base interaction between the phosphonate group of phosphatidylcholine residue and the Lewis acid sites of magnesia-zirconia composite.The infrared absorption spectrum and X-ray photoelectron spectrum of the stationary phase illustrated that the magnesia-zirconia composite was successfully modified with phosphatidylcholine.The interactions between the membrane and the drugs were evaluated.It is observed that the log Kmbm values have good relationships with the log Papp,and the linear slope is 1.049,which is near unity.Moreover,on the basis of the thermodynamics derivation,the difference in standard free energies（Δ（ΔG°））is introduced to describe the drug-membrane interaction.The results show that the log Kmbm and Δ（ΔG°）value provide key information on the transport properties of the drugs.The establishment of this chromatographic model may be a new way for the evaluation of the drug-membrane interactions.