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Multilamellar Liposomes and Solid-Supported Lipid Membranes (TRANSIL): Screening of Lipid-Water Partitioning Toward a High-Throughput Scale

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Abstract

Purpose. 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.

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Authors and Affiliations

  1. Nimbus Biotechnologie GmbH, Eilenburger Str. 4, 04317, Leipzig, Germany

    Angelika Loidl-Stahlhofen, Thorsten Hartmann, Matthias Schöttner, Cornelia Röhring, Hanna Brodowsky & Johannes Schmitt

  2. Bayer AG Pharmaceutical Research, 42096, Wuppertal, Germany

    Jörg Keldenich

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  1. Angelika Loidl-Stahlhofen
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Loidl-Stahlhofen, A., Hartmann, T., Schöttner, M. et al. Multilamellar Liposomes and Solid-Supported Lipid Membranes (TRANSIL): Screening of Lipid-Water Partitioning Toward a High-Throughput Scale. Pharm Res 18, 1782–1788 (2001). https://doi.org/10.1023/A:1013343117979

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