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


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-12

AUTHORS

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

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. More... »

PAGES

1782-1788

Identifiers

URI

http://scigraph.springernature.com/pub.10.1023/a:1013343117979

DOI

http://dx.doi.org/10.1023/a:1013343117979

DIMENSIONS

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PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11785701


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43 schema:description 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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