Preparation of a biomimetic polyphosphorylcholine monolithic column for immobilized artificial membrane chromatography

In vitro membrane binding and protein binding (IAM MB/PB technology) to estimate in vivo distribution: applications in early drug discovery

“…There are several publications establishing the usefulness of the IAM MB/PB technology to model in vivo drug distribution, such as the volume of distribution model [42], unbound volume of distribution model [43][44] and how they can be used to screen compounds in early drug discovery [45]. It was found that strong IAM MB (CHI IAM > 50) can be related to phospholipidosis [46][47], as well as high volume of distribution and tissue partitioning [43].…”

Separation of deamidated peptides with mixed-mode chromatography using phospholipid-functionalized monolithic stationary phases

“…All monolithic columns reported in this study were fabricated in our lab [11,12,[15][16][17][18], and their functional groups can be seen in Fig. S2.…”

“…It has been reported that both hydrophobic and electrostatic interactions may contribute to the retention of charged analytes (such as charged drugs, intact proteins, etc.) on phospholipid-functionalized monoliths [9,11,12,18]. Therefore, several single phospholipid or mixed phospholipid-functionalized monoliths, including the poly (MDPC-co-EDMA), poly (MDPS-co-EDMA), poly (MDPC 90 PS 10 -co-EDMA) and poly (MDPC 60 PA 40 -co-EDMA) monoliths, were selected for the separation of the triad of peptides.…”

“…Recently, a series of phospholipid-functionalized monoliths were developed for studying drug-membrane interactions [9][10][11] and predicting the phospholipidosis-inducing risk of drug candidates [12]. Moreover, these bio-membrane mimicking monoliths exhibited good separation ability for a wide range of compounds including small molecules, peptides, and intact proteins [9,11,13,14] owing to their mixed-mode interactions. Therefore, it is of interest to investigate the applicability of these phospholipidfunctionalized monoliths for the separation of deamidation related residues of mAbs.…”

Controlling selectivity of polymer-based monolithic stationary phases

“…Phoshorylcholine monolith allowed a separation of small hydrophilic peptides, which was not observed on a sulfobetaine‐based monolithic column , which might be probably attributed to a better biocompatibility of choline functionality. Indeed, phosphatidylcholine modified monolithic stationary phases were successfully used as immobilized artificial membranes . After chain‐end n ‐butyl group is introduced in zwitterionic functional group, higher selectivity and efficiency is achieved when compared to classical phoshorylcholine methacrylate with ethyl end group .…”