title: Multilamellar liposomes and solid-supported lipid membranes (TRANSIL): screening of lipid-water partitioning toward a high-throughput scale.
abstract: 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.
authors.affiliation: Nimbus Biotechnologie GmbH, Leipzig, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Loidl-Stahlhofen
authors.forename: T
authors.initials: T
authors.lastname: Hartmann
authors.forename: M
authors.initials: M
authors.lastname: Schöttner
authors.forename: C
authors.initials: C
authors.lastname: Röhring
authors.forename: H
authors.initials: H
authors.lastname: Brodowsky
authors.forename: J
authors.initials: J
authors.lastname: Schmitt
authors.forename: J
authors.initials: J
authors.lastname: Keldenich
mesh_terms: 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
chemical_list: D008051:Lipid Bilayers; D008055:Lipids; D008081:Liposomes; D008567:Membranes, Artificial; D004364:Pharmaceutical Preparations; D014867:Water