Multilamellar liposomes and solid-supported lipid membranes (TRANSIL): screening of lipid-water partitioning toward a high-throughput scale.
OBJECTIVE
Lipid-water partitioning of 187 pharmaceuticals has been assessed with solid-supported lipid membranes (TRANSIL) in microwell plates and with multilamellar liposomes for a data comparison. The high-throughput potential of the new approach was evaluated.


METHODS
Drugs were incubated at pH 7.4 with egg yolk lecithin membranes either on a solid support (TRANSIL beads) or in the form of multilamellar liposomes. Phase separation of lipid and water phase was achieved by ultracentrifugation in case of liposomes or by a short filtration step in case of solid-supported lipid membranes.


RESULTS
Lipid-water partitioning data of both approaches correlate well without systematic deviations in the investigated lipophilicity range. The solid-supported lipid membrane approach provides high-precision data in an automated microwell-plate setup. The lipid composition of the solid-supported lipid membranes was varied to study the influence of membrane change on lipid-water partitioning. In addition, pH-dependent measurements have been performed with minimal experimental effort.


CONCLUSIONS
Solid-supported lipid membranes represent a valuable tool to determine physiologically relevant lipid-water partitioning data of pharmaceuticals in an automated setup and is well suited for high-throughput data generation in lead optimization programs.
Loidl-Stahlhofen
A
A
Nimbus Biotechnologie GmbH, Leipzig, Germany.
Hartmann
T
T
Schöttner
M
M
Röhring
C
C
Brodowsky
H
H
Schmitt
J
J
Keldenich
J
J
D002851:Chromatography, High Pressure Liquid; D008051:Lipid Bilayers / Q000737:chemistry*; D008055:Lipids; D008081:Liposomes; D008567:Membranes, Artificial; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D014867:Water
D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014867:Water