Preparation of a Biomimetic Poly-Phosphatidylserine Monolithic Column for Immobilized Artificial Membrane Chromatography

The pharmacokinetic properties of drugs are significantly influenced by their interactions with cell membranes. Phosphatidylserine (PS) as one of the crucial membrane phospholipids is present abundantly in biological cells. In this study, a PS-mimicking phospholipid membrane polymer monolithic column was developed using the synthetic compound 2-methylacryloxydodecyl phosphatidylserine (MDPS). The physicochemical properties and chromatographic performance of the poly(MDPS-co-ethylene dimethacrylate (EDMA)) monolithic column were evaluated through scanning electron microscopy (SEM) and nano-high-performance liquid chromatography (HPLC). The retention mechanism was investigated by eluting the acidic, neutral, and basic compounds under the same gradient conditions, and the performance of the poly(MDPS-co-EDMA) monolithic column was compared with that of a poly(12-methacryloyl n-dodecylphosphocholine (MDPC)-co-EDMA) monolithic column. The poly(MDPS-co-EDMA) column demonstrated effective separation capabilities for small peptides, protein enzymatic hydrolysis polypeptides, and pharmaceutical compounds. Furthermore, the column was also employed to predict the blood–brain barrier (BBB) permeability of drugs, and the correlation coefficient of 0.73 indicates the promising potential of poly(MDPS-co-EDMA) monolithic column for predicting the ability of drugs to cross the BBB.