School of Chemistry and Chemical Engineering, Chongqing University, Chongqing, P. R. China.
Electrophoresis. 2021 Aug;42(14-15):1436-1449. doi: 10.1002/elps.202000382. Epub 2021 May 9.
Profiling of lipid-water partition coefficients (K ) of drugs is an essential issue during the early stage of drug development. In this study, two liposomes, including 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) + cholesterol (Chol) (DSPC/Chol liposomes) and soybean lecithin (SPC) + Chol (SPC/Chol liposomes), were prepared for the liposome electrokinetic chromatography (LEKC) analysis, and the logarithm of lipid-water partition coefficients (log K ) of neutral and ionic drugs were determined based on an iterative method. The log K values determined by the SPC/Chol or DSPC/Chol liposomes LEKC were linearly fitted, which showed a good fitting coefficient (R = 0.89). Furthermore, the linear relationship between the data obtained from LEKC system and octanol-water system, immobilized artificial membrane, Caco-2 cell model, and software prediction was analyzed, respectively. Results illustrated that DSPC/Chol liposomes or SPC/Chol liposomes had a good linear relationship with Caco-2 cell model, and R was 0.81 and 0.72, respectively. Moreover, the linear free energy relationship analysis suggested that the solute volume, hydrogen bond basicity, and J were the main descriptors that drove the partition process of solutes in the SPC/Chol or DSPC/Chol LEKC system. In addition, the normalized properties of the SPC/Chol and DSPC/Chol LEKC systems through linear free energy relationship analysis were very close. In short, DSPC/Chol liposomes are more suitable for simulating cell membranes than SPC/Chol liposomes, and the developed LEKC is an effective partitioning model for measuring the log K of drugs.
药物的油水分配系数（K）谱分析是药物开发早期的重要问题。在这项研究中，我们制备了两种脂质体，包括 1,2-二硬脂酰-sn-甘油-3-磷酸胆碱（DSPC）+胆固醇（Chol）（DSPC/Chol 脂质体）和大豆卵磷脂（SPC）+Chol（SPC/Chol 脂质体），用于脂质体电动色谱（LEKC）分析，并基于迭代法确定中性和离子药物的油水分配系数（log K）的对数值。通过 SPC/Chol 或 DSPC/Chol 脂质体 LEKC 确定的 log K 值进行线性拟合，结果显示拟合系数（R = 0.89）良好。此外，还分别分析了 LEKC 系统与辛醇-水系统、固定化人工膜、Caco-2 细胞模型和软件预测得到的数据之间的线性关系。结果表明，DSPC/Chol 脂质体或 SPC/Chol 脂质体与 Caco-2 细胞模型具有良好的线性关系，R 值分别为 0.81 和 0.72。此外，线性自由能关系分析表明，溶质体积、氢键碱性和 J 是驱动溶质在 SPC/Chol 或 DSPC/Chol LEKC 系统中分配过程的主要描述符。此外，通过线性自由能关系分析，SPC/Chol 和 DSPC/Chol LEKC 系统的归一化性质非常接近。总之，DSPC/Chol 脂质体比 SPC/Chol 脂质体更适合模拟细胞膜，开发的 LEKC 是测量药物 log K 的有效分配模型。
